Anti-DBH-SAP References

Cat #IT-03


Yun-Fei L, Zhang J, Wang XQ, Peng JJ, Ling BF, Liu FT, Yang F, Dong G, Yu YQ (2022) Noradrenergic innervations of the medial prefrontal cortex mediate empathy for pain in rats via the α1 and β receptors. Behav Brain Res 10:113828. doi: 10.1016/j.bbr.2022.113828

Objective: To study the roles of the locus coeruleus (LC) to medial prefrontal cortex (mPFC) pathway in pain empathy in rats.
Summary: Results indicate that noradrenergic innervations in the mPFC mediate empathy for pain in rats via the α1 and β receptors.
Dose: Noradrenergic innervations of the mPFC were selectively eliminated through intra-mPFC injections of Anti-DBH-SAP.


Aikins A, Little J, Cunningham, J (2021) Role of A1/A2 Neurons in the Dysregulation of Vasopressin Release and Dilutional Hyponatremia in Liver Disease. FASEB J 35(1):. Experimental Biology 2021 Meeting Abstracts doi: 10.1096/fasebj.2021.35.S1.04975

Summary: Experiments suggests that A1/A2 neurons could be involved in the increased plasma AVP seen in male BDL rats as well as the decreased plasma osmolality.
Dose: Selective lesioning of the supraoptic nucleus (SON)-projecting A1/A2 norepinephrine neurons was achieved using anti-DβH-SAP.

Kawanabe R, Yoshihara K, Hatada I, Tsuda M (2021) Activation of spinal dorsal horn astrocytes by noxious stimuli involves descending noradrenergic signaling. Mol Brain 14(1):79. doi: 10.1186/s13041-021-00788-5

Summary: Astrocytes are critical regulators of neuronal function in the central nervous system (CNS). Astrocytes in the spinal dorsal horn (SDH) increase intracellular Ca2+ levels following intraplantar injection of the noxious irritant, formalin, however the underlying mechanisms remain unknown. The authors investigated these mechanisms by focusing on the role of descending noradrenergic (NAergic). Activation of α1A-adrenaline receptors via descending LC-NAergic signals may be a common mechanism underlying astrocytic Ca2+ responses in the SDH evoked by noxious stimuli, including chemical irritants
Dose: Intrathecal treatment with Anti-DBH-SAP, which kills SDH-projecting NAergic neurons, attenuates formalin pain (5.0 µg/20 µl; Martin et al., 1999)

Kucharczyk MW, Valiente D, Bannister K (2021) Developments in Understanding Diffuse Noxious Inhibitory Controls: Pharmacological Evidence from Pre-Clinical Research. J Pain Res 14:1083-1095. doi: 10.2147/JPR.S258602

Summary: This review discusses the pharmacological manipulation interrogation strategies that have been used to examine the functionality of diffuse noxious inhibitory controls (DNIC) and descending control of nociception (DCN).
Dose: Anti-DBH-SAP is one of the drugs tested to influence DNIC expression (Table 1). They reference a publication that reported that icv injection of Anti-DBH-SAP abolished DCN expression (Table 2). Anti-DBH-SAP (5 μg/5 μl) was injected in the left ventricle. Lesion of the LC resulted in failure of DNIC, an effect that mimics what is observed behaviorally after chronic TBI. See Irvine et al., 2020.

Llorca-Torralba M, Camarena-Delgado C, Suárez-Pereira I, Bravo L, Mariscal P, Garcia-Partida JA, López-Martín C, Wei H, Pertovaara A, Mico JA, Berrocoso E (2021) Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons. Brain. doi: 10.1093/brain/awab239

Summary: There is strong comorbidity between chronic pain and depression. This study explores how this comorbidity occurs.  The authors refer to published research that shows icv administration of anti-DBH-SAP or intra-LC administration of lidocaine dampened the evoked pain in conditions of long-term nerve-injury. However, icv injection of anti-DBH-SAP disrupts all noradrenergic nuclei (A1-A7), some of which contribute to sensorial hypersensitivity.  See: Brightwell JJ, Taylor BK (2009) Noradrenergic Neurons in the Locus Coeruleus Contribute to Neuropathic Pain. Neuroscience 160:174-185 and Marques-Lopes J, Pinho D, Albino-Teixeira A, Tavares I (2010) The hyperalgesic effects induced by the injection of angiotensin II into the caudal ventrolateral medulla are mediated by the pontine A(5) noradrenergic cell group. Brain Res 1325:41-52.

Marques SM, Naves LM, Silva TME, Cavalcante KVN, Alves JM, Ferreira-Neto ML, de Castro CH, Freiria-Oliveira AH, Fajemiroye JO, Gomes RM, Colombari E, Xavier CH, Pedrino GR (2021) Medullary Noradrenergic Neurons Mediate Hemodynamic Responses to Osmotic and Volume Challenges. Front Physiol 12:649535. doi: 10.3389/fphys.2021.649535

Summary: The study sought to determine the role of noradrenergic neurons in  hypertonic saline infusion (HSI)-induced hemodynamic recovery.  Findings show that together the A1 and A2 neurons are essential to HSI-induced cardiovascular recovery in hypovolemia.
Dose: Medullary catecholaminergic neurons were lesioned by nanoinjection of Anti-DBH-SAP (0.105 ng·nl−1) into A1, A2, or both (LES A1; LES A2; or LES A1+A2, respectively). Sham rats received nanoinjections of unconjugated saporin in the same regions.

Taxini CL, Marques DA, Bícego KC, Gargaglioni LH (2021) A5 noradrenergic neurons and breathing control in neonate rats. Pflugers Arch 473(6):859-872. doi: 10.1007/s00424-021-02550-1

Summary: In this study, the authors  investigated the participation of A5 noradrenergic neurons in neonates (P7-8 and P14-15) in the control of ventilation during hypoxia and hypercapnia. data suggest that noradrenergic neurons of the A5 region in neonate rats do not participate in the control of ventilation under baseline and hypercapnic conditions, but exert an inhibitory modulation on breathing variability under hypoxic challenge in early life (P7-8).
Dose: Anti-DBH-SAP (420 ng/μL) or saporin (SAP, control) was injected into the A5 region of neonatal male Wistar rats.

Thorsdottir DJ (2021) The Role Of Bdnf-Mediated Neuroplasticity In Cardiovascular Regulation Within The Hypothalamus And Brainstem. Univ Vermont, Dept Pharmacology 1387.

Summary: This PhD dissertation to determine the mechanism behind BDNF-mediated cardiovascular regulation.
Dose: Rats received bilateral NTS injections of vehicle or Anti-DBH-SAP, which selectively lesions catecholaminergic neurons. Treatment increased blood pressure in the GFP group but failed to affect blood pressure in the BDNF group.


Boccia L, Le Foll C, Lutz TA. Noradrenaline signaling in the LPBN mediates amylin’s and salmon calcitonin’s hypophagic effect in male rats. (2020) FASEB J 34(11):15448-15461. doi: 10.1096/fj.202001456RRR

Objective: To assess the phenotype of amylin activated LPBN (lateral parabrachial nucleus) neurons, especially to confirm the CGRPergic phenotype and to uncover the specific role of NA (noradrenaline) signaling from the AP to the LPBN.
Summary: The present study confirmed the central role of the LPBN in propagating amylin’s and sCT’s hypophagic action, and particularly the importance of AP → LPBN NA signaling in the mediation of this process, through the activation of LPBN (CGRP and non-CGRP) neurons.
Dose: A specific lesion of about half of the total AP NA population with the immunotoxin anti-DBH-SAP) was sufficient to abolish the hypophagic effect of amylin in rats and also reduced amylin’s ability to induce c-Fos expression in AP neurons. The neuronal pathways used to process the physiological response to amylin were investigated using 50-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the area postrema (AP) or 25 ng into the lateral parabrachial nucleus (Potes et al., 2010).

Herman JP (2020) Corticolimbic stress regulatory circuits, hypothalamo–pituitary–adrenocortical adaptation, and resilience. Chen A (Ed.): Stress Resilience 291-309. Academic Press doi: 10.1016/B978-0-12-813983-7.00019-7

Summary: Review. Immunolesion of paraventricular nucleus (PVN)-projecting norepinephrine (NE) neurons with Anti-DBH-SAP attenuates acute stress reactivity (interestingly, to restraint), but it does not inhibit somatic or HPA axis responses to stress in any simple way (Flak et al., 2014). PVN-projecting norepinephrine (NE) neurons appear to be responsible for acute responses to systemic stressors, but they do not appear to be important in mediating effects of chronic stress (Ritter et al., 2003).
Dose: Flak et al. injected 8.82 ng of Anti-DBH-SAP into the PVN.  Ritter et al. injected 42 ng into the PVN.

Irvine KA, Sahbaie P, Ferguson AR, Clark JD (2020) Loss of diffuse noxious inhibitory control after traumatic brain injury in rats: A chronic issue. Exp Neurol 333:113428. doi: 10.1016/j.expneurol.2020.113428

Summary: The authors hypothesize that dysfunctional descending noradrenergic and serotonergic pain control circuits may contribute to the loss of diffuse noxious inhibitory control (DNIC), a critical endogenous pain control mechanism, weeks to months after traumatic brain injury (TBI). Results suggest that TBI causes maladaptation of descending nociceptive signaling mechanisms and changes in the function of both adrenergic and serotonergic circuits. Such changes could predispose those with TBI to chronic pain. Dose: Anti-DBH-SAP (5 μg/5 μl) was injected in the left ventricle. Lesion of the LC resulted in failure of DNIC, an effect that mimics what is observed behaviorally after chronic TBI.

Patrone LGA, Capalbo AC, Marques DA, Bícego KC, Gargaglioni LH. An age- and sex-dependent role of catecholaminergic neurons in the control of breathing and hypoxic chemoreflex during postnatal development. (2020) Brain Res 1726:146508. doi: 10.1016/j.brainres.2019.146508

Objective:  To discover the role of brainstem catecholaminergic (CA) neurons in the hypoxic ventilatory response (HVR).
Summary:  Brainstem CA neurons modulate the HRV during the postnatal phase, and possibly thermoregulation during hypoxia.
Dose: Evaluation of brainstem CA neurons in the HVR during postnatal development  in male and female rats through specific cell depletion with Anti-DBH-SAP (420 ng/nL) injected in the fourth ventricle.

Ribeiro N, Martins Sá RW, & Antunes VR. Depletion of C1 neurons attenuates the salt-induced hypertension in unanesthetized rats. (2020) Brain Res, 1748:147107. doi: 10.1016/j.brainres.2020.147107

Objective: To determine if the ablation of Cl neurons mitigate the high blood pressure induced by high-salt intake.
Summary: Data show that hypertension induced by high-salt intake is dependent on Cl neurons. 
Dose: Bilateral injections of 2.4 ng/100 nl of Anti-DBH-SAP. The total number of TH+ neurons in the AS region was reduced by 37 ± 13% in the anti-DBH-SAP group when compared to control.  The injection of anti-Df3H-SAP into the RVLM reduced 80% of the TH+ neurons in the total number of Cl neurons, and 38% in the AS region.

Schneider J. Integration of Peripheral and Central Systems in Control of Ingestive and Reproductive Behavior (2020) Oxford University Press. doi: 10.1093/acrefore/9780190264086.013.23

Summary: Highly glucose-sensitive cells in the ventrolateral medulla send catecholaminergic projections to the PVH. These projections can be selectively destroyed by Anti-DBH-SAP “DSAP” lesions, wherein a toxin (saporin) is directed at nondopaminergic cells that express the enzyme necessary for synthesis of epinephrine and norepinephrine (the enzyme is dopamine beta hydroxylase). DSAP experiments show that catecholaminergic projections from glucose-sensitive cells in the ventrolateral medulla are necessary for all responses to glucoprivation, including increases in epinephrine secretion, glucocorticoid secretion, sex behavior, and food intake (reviewed by Ritter et al., 2019).

Tapa S, Wang L, Francis Stuart SD, Wang Z, Jiang Y, Habecker BA, Ripplinger CM (2020) Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss. Sci Rep 10:18801. doi: 10.1038/s41598-020-75903-y

Summary: The authors present a novel mouse model of regional cardiac sympathetic hypo-innervation utilizing Anti-DBH-SAP.
Dose: Either 5μL of 40 ng/μL  Anti-DBH-SAP or Mouse IgG-SAP (control) was applied three times directly to the exposed apical/anterior surface of the heart.

Vasquez JH, Borniger JC (2020) Neuroendocrine and Behavioral Consequences of Hyperglycemia in Cancer. Endocrinology 161(5):bqaa047. doi: 10.1210/endocr/bqaa047

Summary: Ablation of norepinephrine containing projections to the arcuate (via saporin-conjugated antidopamine beta-hydroxylase injections) alters AgRP and NPY concentrations, leading to impairments in hypoglycemic (glucoprivic) or ghrelin-induced feeding.
Dose: Anti-DBH-SAP (bilateral 42-ng intracranial injections) was used in rats to investigate the role of hindbrain catecholamine afferents in increased ARC NPY and AGRP gene expression (Fraley et al., 2003).


Andrade DC, Toledo C, Díaz HS, Lucero C, Arce-Álvarez A, Oliveira LM, Takakura AC, Moreira TS, Schultz HD, Marcus NJ, Alcayaga J, Del Rio R. Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure. (2019) Clin Sci (Lond) 133(3):393-405. doi: 10.1042/CS20180589

Objective: To determine the role played by RVLM-C1 neurons in cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction in volume overload-induced heart failure.
Summary: RVLM-C1 neurons were selectively ablated using Anti-DβH-SAP and measures of cardiacautonomictone, function, and arrhythmia incidence were evaluated.  Cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction were present in HF rats and improved after Anti-DβH-SAP treatment.
Dose: (7.5ng/100nl of sterile saline solution) was injected bilaterally into the RVLM.

Bahari Z, Meftahi GH. Spinal α2 -adrenoceptors and neuropathic pain modulation; therapeutic target. (2019) Br J Pharmacol 176(14):2366-2381. doi: 10.1111/bph.14580

Objective: To provide an an overview of the cellular mechanisms through which brainstem adrenergic descending inhibitory processing can alter spinal pain transmission to the higher centres, and how these pathways change in neuropathic pain conditions focusing on the role of spinal α2‐adrenoceptors in the spinal dorsal horn.
Summary: The α2‐adrenoceptor agonist may be useful to treat neuropathic pain

Deura C, Minabe S, Ikegami K, Inoue N, Uenoyama Y, Maeda KI, Tsukamura H. Morphological analysis for neuronal pathway from the hindbrain ependymocytes to the hypothalamic kisspeptin neurons. (2019) J Reprod Dev 65(2):129-137. doi: 10.1262/jrd.2018-122

Objective: To examine the existence of a neuronal pathway from the hindbrain ependymocytes to kisspeptin neurons in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV).
Summary: The hindbrain ependymocytes have neuronal connections with the kisspeptin neurons, most probably via hindbrain noradrenergic and CRH neurons to relay low energetic signals for regulation of reproduction.
Cites I’Anson H, Sundling LA, Roland SM, Ritter S. Endocrinology 2003; 144: 4325–4331.

Devoto P, Flore G, Saba P, Scheggi S, Mulas G, Gambarana C, Spiga S, Gessa GL. Noradrenergic terminals are the primary source of α2-adrenoceptor mediated dopamine release in the medial prefrontal cortex. (2019) Prog Neuropsychopharmacol Biol Psychiatry 90:97-103. doi: 10.1016/j.pnpbp.2018.11.015

Objective: To clarify the relative contribution of dopamine (DA) release from noradrenergic and dopaminergic terminals to DA output induced by blockade of α2-adrenoreceptors and the norepinephrine transporter.

Katsurada K, Nakata M, Saito T, Zhang B, Maejima Y, Nandi SS, Sharma NM, Patel KP, Kario K, Yada T. Central Glucagon-like Peptide-1 Receptor Signaling via Brainstem Catecholamine Neurons Counteracts Hypertension in Spontaneously Hypertensive Rats. (2019) Sci Rep 9(1):12986. doi: 10.1038/s41598-019-49364-x

Objective: To determine mechanisms for antihypertensive effect of GLP-1R agonists.
Summary: The central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity.
Dose: Anti-DBH-SAP or Blank-SAP was injected into NTS bilaterally (6 ng/200 nl).

Murtazina AR, Nikishina YO, Dil’mukhametova LK, Sapronova AY, Ugrumov MV. The Role of the Brain in the Regulation of Peripheral Noradrenaline-producing Organs in Rats During Morphogenesis. (2019) Dokl Biochem Biophys 486(1):243-246. doi: 10.1134/S1607672919030207

Ritter S, Li A-J, & Wang Q. Hindbrain glucoregulatory mechanisms: Critical role of catecholamine neurons in the ventrolateral medulla. (2019) Physiol Behav 208:112568. doi: 10.1016/j.physbeh.2019.112568

IT-03:  Anti-DBH-SAP and IT-28:  NPY-SAP – REVIEW
Objective:  To explore circuitry and potential glucose-sensing mechanisms that contribute to the functions of glucoregulatory catecholamine neurons in the ventrolateral medulla
Summary:  Selective lesion of hindbrain catecholamine neurons abolishes glucoprivic elicitation of key counterregulatory responses. Selective chemogenetic activation of specific catecholamine populations elicits these responses.

Thorsdottir D, Cruickshank NC, Einwag Z, Hennig GW, Erdos B. BDNF downregulates β-adrenergic receptor-mediated hypotensive mechanisms in the paraventricular nucleus of the hypothalamus. (2019) Am J Physiol Heart Circ Physiol. 317(6):H1258-H1271. doi: 10.1152/ajpheart.00478.2019

Objective:  To determine whether BDNF increases blood pressure in part by diminishing inhibitory hypotensive input from nucleus of the solitary tract (NTS) catecholaminergic neurons projecting to the PVN.
Summary:  BDNF, a key hypothalamic regulator of blood pressure, disrupts catecholaminergic  signaling between the NTS and the PVN by reducing the responsiveness of PVN neurons to inhibitory hypotensive β-adrenergic input from the NTS.
Dose:  Bilateral NTS injections of sterile PBS (for control) or Anti-DBH-SAP (22 ng).

Toledo C, Andrade DC, & Del Rio R. Brainstem pre-sympathetic neurons contribute to irregular breathing patterns in volume overload heart failure. (2019) FASEB J, 33:lb630-lb630. . doi: 10.1096/fasebj.2019.33.1_supplement.lb630

Objective: To investigate the contribution of RVLM-C1 neurons on breathing disorders in chronic heart failure (CHF).
Summary: RVLM-C1 neurons play a critical role in the maintenance of altered breathing patterns in CHF rats and highlighted their contribution to the worsening of cardiac function during central chemoreflex activation. DBH-SAP treatment decreased active expiration in CHF rats and deleterious effects of central chemoreflex activation on diastolic cardiac function and cardiac autonomic control were blunted.
Dose: Stereotaxic bilateral injections of Anti-DBH-SAP (5 ng/150 nl).

Toledo C, Andrade DC, Díaz HS, Pereyra KV, Schwarz KG, Díaz-Jara E, Oliveira LM, Takakura AC, Moreira TS, Schultz HD, Marcus NJ, Del Rio R. Rostral ventrolateral medullary catecholaminergic neurones mediate irregular breathing pattern in volume overload heart failure rats. (2019) J Physiol 597(24):5799-5820. doi: 10.1113/JP278845

Objective:  To investigate the potential contribution of RVLM‐C1 neurons to irregular breathing.
Summary:  Findings suggest that RVLM‐C1 neurons play a pivotal role in breathing irregularities in volume overload HF, and mediate the sympathetic responses induced by acute central chemoreflex activation.
Dose:  Bilateral injections of Anti-DBH-SAP (7.5ng/100nl of sterile saline solution) delivered to the RVLM-C1 region.  Reduction (65%) of RVLM‐C1 neurons resulted in attenuation of irregular breathing, decreased apnea‐hypopnea incidence and improved cardiac autonomic control.

Urquhart MA, Ross JA, Reyes BAS, Nitikman M, Thomas SA, Mackie K, & Van Bockstaele EJ. Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex. (2019) Neurobiology of Stress 10:100164. doi: 10.1016/j.ynstr.2019.100164

Objective:  To determine the effects of NE depletion on the eCB system.
Summary:  The results suggest that the endocannabinoids (eCB) system may be more responsive in males than females under conditions of NE perturbation, thus having potential implications for sex-specific treatment strategies of stress-related psychiatric disorders.
Dose:  The authors used a DBH knockout model and DSP-4 (a compound that depletes endogenous norepinephrine and enhances release of [3H]norepinephrine).  More specific mechanisms for further corroboration could be undertaken, such as using Anti-DBH-SAP to provide a more complete lesion compared to DSP-4.

Verkhratsky A, Parpura V, Rodriguez-Arellano J, & Zorec R. Astroglia in Alzheimer’s Disease. (2019) In: Verkhratsky A, Ho M, Zorec R, Parpura V (eds) Neuroglia in Neurodegenerative Diseases. Advances in Experimental Medicine and Biology, 1175:273-324. Springer, Singapore. doi: 10.1007/978-981-13-9913-8_11

IT-01:  192-IgG-SAP and IT-03:  Anti-DBH-SAP
Summary:  A review of the tools for creating animal models of Alzheimer’s Disease.  192-IgG-SAP binds selectively and irreversibly to low-affinity nerve growth factor receptor interrupting cholinergic neuronal protein synthesis was employed.  Anti-DBH-SAP binds dopamine-β-hydroxylase, which is not only localized mainly in the cytosol, but also at the plasma membrane surface of noradrenergic neurons.  Anti-DBH-SAP produced specific and dose-dependent depletions of locus coeruleus neurons, with no effects on other cholinergic, dopaminergic or serotonergic neuronal populations.  The possibility to induce a partial or total noradrenergic loss (by varying the injected dose) makes this immunotoxic approach an ideal model to study events within the noradrenergic projection system, as they occur during age-related demise of locus coeruleus in humans.


Ermine CM, Wright JL, Frausin S, Kauhausen JA, Parish CL, Stanic D, Thompson LH. Modelling the dopamine and noradrenergic cell loss that occurs in Parkinson’s disease and the impact on hippocampal neurogenesis. (2018) Hippocampus 28(5):327-337. doi: 10.1002/hipo.22835

Objective: The mechanisms underlying reduced neurogenesis in Parkinson’s Disease (PD) are not well established. The authors tested the hypothesis that noradrenergic and dopaminergic depletion, as occurs in PD, impairs hippocampal neurogenesis.
Summary: Mechanisms of neurotransmitter-based regulation of cognition and hippocampal neurogenesis may well overlap under certain conditions but the present results do not suggest a simple relationship associated with the degeneration of the two most prominently affected transmitter systems in PD.
Dose: Rats received 1 mcg Anti-DBH-SAP icv.

Leanza G, Gulino R, Zorec R. Noradrenergic Hypothesis Linking Neurodegeneration-Based Cognitive Decline and Astroglia. (2018) Front Mol Neurosci 11:254. doi: 10.3389/fnmol.2018.00254

Objective:  To examine noradrenergic dysfunction in AD-related cognitive decline in humans and its potential involvement in AD pathology and disease progression.
Summary:  The authors discuss noradrenergic dysfunction in AD-related cognitive decline.  The research focuses on animal models to allow the validation of the noradrenergic hypothesis of AD, including those based upon the Anti-DBH-SAP-mediated ablation of LC.  The article also addresses how astrocytes may participate in the regulation of neurogenesis, a new strategy for preventing LC neuron loss.
Dose:  DBH (–/–) knockout mice do not seem to offer the possibility to obtain partial or graded neurotransmitter depletions. In light of these limitations, the authors used Anti-DBH-SAP which is able to target noradrenergic neurons in the LC with unprecedented selectivity and efficiency.  Anti-DBH-SAP was injected bilaterally into the LC.

Lee SJ, Jokiaho AJ, Sanchez-Watts G, Watts AG. Catecholaminergic Projections into an Interconnected Forebrain Network Control the Sensitivity of Male Rats to Diet-Induced Obesity (2018) Am J Physiol Regul Integr Comp Physiol 314(6):R811-R823. doi: 10.1152/ajpregu.00423.2017

Objective:  To investigate the role of hindbrain catecholamine neuron pathways and their contribution to long-term energy homeostasis by controlling obesogenic sensitivity to a high-fat, high sucrose choice diet.
Summary:  The authors show that catecholamine neurons (primarily in the VLM and NTS) convey essential feedback signals to enable long-term adaptive control of energy metabolism when animals consume a predominantly carbohydrate diet.  This is the first report specifically associating this projection system with the long-term control of adiposity.
Dose: (Cat. #KIT-03; Anti-DBH-SAP and IT-18; Mouse IgG-SAP).  Catecholaminergic projections to the PVH and related parts of the forebrain were lesioned with bilateral injections each consisting of 42 ng/200 nL of Anti-DBH-SAP or equimolar amounts of control Mouse IgG-SAP.

Naves LM, Marques SM, Mourão AA, Fajemiroye JO, Xavier CH, de Castro CH, Rebelo ACS, Rosa DA, Gomes RM, Colombari E, & Pedrino GR. Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats. (2018). Scientific Reports, 8 (1):11276.

Objective:  To evaluate the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats.
Summary: The recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.
Dose:  In order to achieve A1 and/or A2 neuronal lesions, Anti-DBH-SAP (100 nL, 0.105 ng·nL−1 ) was nanoinjected into the CVLM and NTS region, respectively.  In sham groups, the equimolar of Saporin (100 nL, 0.022 ng·nL−1 ) was nanoinjected into the same site.

Patrone LGA, Biancardi V, Marques DA, Bícego KC, Gargaglioni LH. Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats. (2018) J Physiol 596(15):3299-3325. doi: 10.1113/JP275731

Objective:  To determine the role of the brainstem CA system in ventilatory control under normocapnic and hypercapnic conditions during different phases of development (P7-8, P14-15 and P20-21) in male and female Wistar rats.
Summary:  Brainstem CA neurones produce a tonic inhibitory drive that affects breathing frequency in P7-8 rats and provide an inhibitory drive during hypercapnic conditions in both males and females at P7-8 and P14-15.
Dose:  Anti-DBH-SAP (420 ng/μL – 1 μL for P0-1; 1.5 μL for P7-8; 2.0 μL for P13-14) was injected into the 4th ventricle of neonatal Wistar rats of both sexes.  Control rats were injected with vehicle (PBS, 0.01 M, pH 7.4) or unconjugated saporin (Cat. #PR-01), with respective volumes for each age, as described for the Anti-DBH-SAP group. All injections were performed using a microinjector pump over a period of 5 min to allow drug diffusion.

Pintus R, Riggi M, Cannarozzo C, Valeri A, de Leo G, Romano M, Gulino R, & Leanza G. Essential Role of Hippocampal Noradrenaline in the Regulation of Spatial Working Memory and Tdp‐43 Tissue Pathology. (2018). Journal of Comparative Neurology, 526 (7):1131-1147.

Objective: To determine the noradrenergic contribution to cognitive and histopathological changes in Alzheimer’s Disease.
Summary: Integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP-43 tissue pathology.
Dose: Anti-DBH-SAP was used at a dose of 0.50 µg dissolved in sterile PBS.

POSTER:  Sanvanson P, Li Z, Ward BD, & Shaker R. Mo1545 – Vagal Nerve Modulates the Effects of Esophageal Acid on the Periaqueductal Gray Functional Connectivity in a Rat Model. (2018). Gastroenterology, 154 (6, Supplement 1):S-747-S-748.

Winston J (2018) Mo1546 – Neonatal Colon Inflammation-Induced Increases in Pituitary Adenylate Cyclase Activating Peptide Expression in the Parabrachial Nucleus Contributes to Reduced Meal Consumption, to Increased Meal-Induced Aversive and Anxiety-Like Behaviors in Adult Rats. Gastroenterology 154:S-748. doi: 10.1016/S0016-5085(18)32597-6

Summary: Infusion of Anti-DBH-SAP into the dorsal vagal complex significantly increased meal volumes and increased open field activity compared to IgG-saporin treatment.


Benn A, Robinson ES. (2017) Differential Roles for Cortical Versus Sub-Cortical Noradrenaline and Modulation of Impulsivity in the Rat. Psychopharmacology (Berl) 234(2):255-66. PMID: 27744551 (Targeting Trends 17q1)

Bondarenko NS, Dilmukhametova LK, Kurina AY, Murtazina AR, Sapronova AY, Sysoeva AP, Ugrumov MV. (2017) Plasticity of Central and Peripheral Sources of Noradrenaline in Rats During Ontogenesis. Biochemistry (Mosc) 82(3):373-79. PMID: 28320279

Malheiros-Lima MR, Takakura AC, Moreira TS. (2017) Depletion of Rostral Ventrolateral Medullary Catecholaminergic Neurons Impairs the Hypoxic Ventilatory Response in Conscious Rats. Neuroscience 351:1-14. PMID: 28363783

Murtazina AR, Dilmukhametova LK, Nikishina YO, Sapronova AY, Volina EV, Ugrumov MV. Changes in the secretory activity of organs producing noradrenaline upon inhibition of its synthesis in neonatal rat brain (2017) Russ J Dev Biol 48:295-300. doi: 10.1134/S1062360417050058

Taxini CL, Moreira TS, Takakura AC, Bícego KC, Gargaglioni LH, Zoccal DB. (2017) Role of A5 Noradrenergic Neurons in the Chemoreflex Control of Respiratory and Sympathetic Activities in Unanesthetized Conditions. Neuroscience 354:146-57. PMID: 28461215 (read summary)


Arora V, Morado-Urbina CE, Aschenbrenner CA, Hayashida K, Wang F, Martin TJ, Eisenach JC, Peters CM. (2016) Disruption of Spinal Noradrenergic Activation Delays Recovery of Acute Incision-Induced Hypersensitivity and Increases Spinal Glial Activation in the Rat. J Pain 17(2):190-202. PMID: 26545342 (Targeting Trends 16q1)

Coradazzi M, Gulino R, Fieramosca F, Falzacappa LV, Riggi M, Leanza G. (2016) Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis. Neurobiol Aging 48:93-102. PMID: 27644078 (Targeting Trends 16q4)

Jokiaho A, Watts AG (2016) Catecholaminergic innervation and the neuronal activation of hypothalamic glucose sensitive regions during rapid- and slow-onset hypoglycemia in adult male rats. Soc Neurosci Meeting Abstract 256.21

Kaushal R, Taylor BK, Jamal AB, Zhang L, Ma F, Donahue R, Westlund KN. (2016) GABA-A receptor activity in the noradrenergic locus coeruleus drives trigeminal neuropathic pain in the rat; contribution of NAalpha1 receptors in the medial prefrontal cortex. Neuroscience 334:148-159. PMID: 27520081 (Targeting Trends 16q4)

Kelly SC, Nelson PT, Counts SE (2016) The locus coeruleus: a potential link between cerebrovascular and neuronal pathology in Alzheimer’s disease. Soc Neurosci Meeting Abstract 786.11

Lee SJ, Diener K, Kaufman S, Krieger JP, Pettersen KG, Jejelava N, Arnold M, Watts AG, Langhans W. (2016) Limiting glucocorticoid secretion increases the anorexigenic property of Exendin-4. Mol Metab 5(7):552-565. PMID: 27408779 (Targeting Trends 16q4)

Mohammed M, Kulasekara K, Ootsuka Y, Blessing WW. (2016) Locus coeruleus noradrenergic innervation of the amygdala facilitates alerting-induced constriction of the rat tail artery. Am J Physiol Regul Integr Comp Physiol 310(11):R1109-19. PMID: 27101292 (Targeting Trends 16q3)

Nam H, Kerman IA. (2016) A2 noradrenergic neurons regulate forced swim test immobility. Physiol Behav 165:339-349. PMID: 27553574 (Targeting Trends 16q4)

Schwartz MD, Nguyen AT, Warrier DR, Palmerston JB, Thomas AM, Morairty SR, Neylan TC, Kilduff TS. (2016) Locus Coeruleus and Tuberomammillary Nuclei Ablations Attenuate Hypocretin/Orexin Antagonist-Mediated REM Sleep. eNeuro 3(2) PMID: 27022631 (Targeting Trends 16q2)

Silva TM, Takakura AC, Moreira TS. (2016) Acute Hypoxia Activates Hypothalamic Paraventricular Nucleus-Projecting Catecholaminergic Neurons in the C1 Region. Exp Neurol 285(Pt A):1-11. PMID: 27569537 (Targeting Trends 17q1)

Urquhart M, Reyes BAS, Thomas SA, Mackie K, Van Bockstaele EJ (2016) Diacylglycerol lipase-α expression increases in the coeruleo-cortical pathway in dopamine-β-hydroxylase knockout mice as well as rats treated with DSP-4 Soc Neurosci Meeting Abstract 77.09


Bourassa EA, Stedenfeld KA, Sved AF, Speth RC. (2015) Selective C1 Lesioning Slightly Decreases Angiotensin II Type I Receptor Expression in the Rat Rostral Ventrolateral Medulla (RVLM). Neurochem Res 40(10):2113-2120. PMID: 26138553 (Targeting Trends 15q4)

Burke PG, Kanbar R, Viar KE, Stornetta RL, Guyenet PG. (2015) Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats activates breathing without changing blood pressure or causing arousal or sighs. J Appl Physiol (1985) 118(12):1491-1501. (Targeting Trends 15q3)

Devoto P, Flore G, Saba P, Frau R, Gessa GL. (2015) Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex. Brain Behav 5(10):e00393. PMID: 26516613 (Targeting Trends 16q1)

Freiria-Oliveira AH, Blanch GT, Pedrino GR, Cravo SL, Murphy D, Menani JV, Colombari DS. (2015) Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses. Am J Physiol Regul Integr Comp Physiol 309(9):R1082-91. PMID: 26333788 (Targeting Trends 15q4)

King TL, Ruyle BC, Kline DD, Heesch CM, Hasser EM. (2015) Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia. Am J Physiol Regul Integr Comp Physiol 309(7):R721-31. PMID: 26157062 (Targeting Trends 15q4)

Li AJ, Wang Q, Elsarelli MM, Brown RL, Ritter S. (2015) Hindbrain catecholamine neurons activate orexin neurons during systemic glucoprivation in male rats. Endocrinology 156(8):2807-2820. (Targeting Trends 15q3)

Li AJ, Wang Q, Davis H, Wang R, Ritter S. (2015) Orexin-A Enhances Feeding in Male Rats by Activating Hindbrain Catecholamine Neurons. Am J Physiol Regul Integr Comp Physiol Epub:ajpregu.00065.2015. (Targeting Trends 15q3)

Peters CM, Hayashida K, Suto T, Houle TT, Aschenbrenner CA, Martin TJ, Eisenach JC. (2015) Individual Differences in Acute Pain-induced Endogenous Analgesia Predict Time to Resolution of Postoperative Pain in the Rat. Anesthesiology 122(4):895-907. (Targeting Trends 15q2)


Flak JN, Myers B, Solomon MB, McKlveen JM, Krause EG, Herman JP. (2014) Role of paraventricular nucleus-projecting norepinephrine/epinephrine neurons in acute and chronic stress. Eur J Neurosci 39(11):1903-1911. (Targeting Trends 14q3)

Jokiaho AJ, Donovan CM, Watts AG. (2014) The rate of fall of blood glucose determines the necessity of forebrain-projecting catecholaminergic neurons for male rat sympathoadrenal responses. Diabetes 63(8):2854-2865. (Targeting Trends 15q1)

Li AJ, Wang Q, Dinh TT, Powers BR, Ritter S. (2014) Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 306(4):R257-64. (Targeting Trends 14q2)

Ostock CY, Lindenbach D, Goldenberg AA, Kampton E, Bishop C. (2014) Effects of noradrenergic denervation by anti-DBH-saporin on behavioral responsivity to l-DOPA in the hemi-parkinsonian rat. Behav Brain Res 270C:75-85.

Summary:  Dopamine loss is central to Parkinson’s disease and is often accompanied by noradrenergic denervation of the locus coeruleus. In this work the authors examined the role this loss plays in L-DOPA therapy using a rat Parkinson’s disease model.
Dose:  Rats received 10 μg of anti-DBH-SAP into the left lateral ventricle. Loss of norepinephrine (NE) neurons did not affect behavior, but lesioned animals were less responsive to the pro-motor therapeutic effects of L-DOPA.

Shin E, Rogers JT, Devoto P, Bjorklund A, Carta M. (2014) Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease. Exp Neurol 257C:25-38. (Targeting Trends 14q3)

Suto T, Severino AL, Eisenach JC, Hayashida KI. (2014) Gabapentin increases extracellular glutamatergic level in the locus coeruleus via astroglial glutamate transporter-dependent mechanisms. Neuropharmacology 81C:95-100. (Targeting Trends 14q2)


Chang ST, Liu YP, Huang CL, Wang PY, Tung CS. (2013) Implication of Cerebral Dopamine-beta Hydroxylase for Cardiovascular and Mood Regulation in Rats. Chin J Physiol 56(4) (Targeting Trends 13q4)

da Silva EF, Freiria-Oliveira AH, Custodio CH, Ghedini PC, Bataus LA, Colombari E, de Castro CH, Colugnati DB, Rosa DA, Cravo SL, Pedrino GR. (2013) A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats. PLoS One 8(9):e73187. (Targeting Trends 14q1)

Freiria-Oliveira AH, Blanch GT, De Paula PM, Menani JV, Colombari DS. (2013) Lesion of the commissural nucleus of the solitary tract/A2 noradrenergic neurons facilitates the activation of angiotensinergic mechanisms in response to hemorrhage. Neuroscience 254:196-204. (Targeting Trends 14q1)

Guyenet PG, Stornetta RL, Bochorishvili G, Depuy SD, Burke PG, Abbott SB. (2013) C1 neurons: the body’s EMTs. Am J Physiol Regul Integr Comp Physiol 305(3):R187-204. (Targeting Trends 13q4)

Li AJ, Wang Q, Dinh TT, Wiater MF, Eskelsen AK, Ritter S. (2013) Hindbrain Catecholamine Neurons Control Rapid Switching of Metabolic Substrate Use during Glucoprivation in Male Rats. Endocrinology 154(12):4570-4579. (Targeting Trends 14q1)

Romano A, Potes CS, Tempesta B, Cassano T, Cuomo V, Lutz T, Gaetani S. (2013) Hindbrain noradrenergic input to the hypothalamic PVN mediates the activation of oxytocinergic neurons induced by the satiety factor oleoylethanolamide. Am J Physiol Endocrinol Metab 305(10):E1266-73. (Targeting Trends 14q1)

Talman WT, Lin LH. (2013) Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii. Auton Neurosci 175(1-2):9-16. (Targeting Trends 13q2)

Wenker IC, Sobrinho CR, Takakura AC, Mulkey DK, Moreira TS. (2013) P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure. Hypertension 62(2):263-273. (Targeting Trends 13q4)

Zheng H, Rinaman L. (2013) Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis. Eur J Neurosci 37(8):1340-1349. (Targeting Trends 13q2)


Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. (2012) Control of sleep and wakefulness. Physiol Rev 92(3):1087-1187. (Targeting Trends 12q4)

Daubert DL, McCowan M, Erdos B, Scheuer DA. (2012) Nucleus of the Solitary Tract catecholaminergic neurons modulate the cardiovascular response to psychological stress in rats. J Physiol 590(Pt 19):4881-4895. (Targeting Trends 12q4)

Hayashida K, Peters CM, Gutierrez S, Eisenach JC. (2012) Depletion of Endogenous Noradrenaline Does Not Prevent Spinal Cord Plasticity Following Peripheral Nerve Injury. J Pain 13(1):49-57. (Targeting Trends 12q1)

Kaminski KL, Watts AG. (2012) Intact catecholamine inputs to the forebrain are required for appropriate regulation of corticotrophin-releasing hormone and vasopressin gene expression by corticosterone in the rat paraventricular nucleus. J Neuroendocrinol 24(12):1517-1526. (Targeting Trends 12q4)

Pedrino GR, Freiria-Oliveira AH, Almeida Colombari DS, Rosa DA, Cravo SL. (2012) A2 noradrenergic lesions prevent renal sympathoinhibition induced by hypernatremia in rats. PLoS One 7(5):e37587. (Targeting Trends 12q4)

Pongratz G, Melzer M, Straub RH. (2012) The sympathetic nervous system stimulates anti-inflammatory B cells in collagen-type II-induced arthritis. Ann Rheum Dis 71(3):432-439. (Targeting Trends 11q4)

Smith CD, Holschbach MA, Olsewicz J, Lonstein JS. (2012) Effects of noradrenergic alpha-2 receptor antagonism or noradrenergic lesions in the ventral bed nucleus of the stria terminalis and medial preoptic area on maternal care in female rats. Psychopharmacology (Berl) 224(2):263-276. (Targeting Trends 12q3)

Talman WT, Dragon DN, Jones SY, Moore SA, Lin LH. (2012) Sudden Death and Myocardial Lesions after Damage to Catecholamine Neurons of the Nucleus Tractus Solitarii in Rat. Cell Mol Neurobiol 32(7):1119-1126. (Targeting Trends 12q3)


Abbott SB, Stornetta RL, Coates MB, Guyenet PG. (2011) Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats. J Neurosci 31(45):16410-16422. (Targeting Trends 12q1)

Burke PG, Neale J, Korim WS, McMullan S, Goodchild AK. (2011) Patterning of somatosympathetic reflexes reveals non-uniform organization of presympathetic drive from C1 and non-C1 RVLM neurons. Am J Physiol Regul Integr Comp Physiol 301(4):R1112-R1122. (Targeting Trends 11q4)

Goehler LE, Gaykema RPA. (2011) Targeted Lesion of Caudal Brainstem Catecholamine Neurons Reveals Their Role in Symptoms of Fatigue. Targeting Trends 12(1).

Huckstepp RT, Dale N. (2011) Redefining the components of central CO2 chemosensitivity – towards a better understanding of mechanism. J Physiol 589(Pt 23):5561-5579. (Targeting Trends 12q1)

Khan AM KKL, Sanchez-Watts, Ponzio TA, Kuzmiski JB, Bains JS, Watts AG. (2011) MAP kinases couple hindbrain-derived catecholamine signals to hypothalamic adrenocortical control mechanisms during glycemia-related challenges. J Neurosci 31(50):18479-18491. (Targeting Trends 12q1)

Lee S, Craddock Z, Rivier C. (2011) Brain stem catecholamines circuitry: Activation by alcohol and role in the hypothalamic-pituitary-adrenal response to this drug. J Neuroendocrinol 23(6):531-541. (Targeting Trends 11q2)

Li AJ, Wang Q, Ritter S. (2011) Participation of hindbrain AMP-activated protein kinase in glucoprivic feeding. Diabetes 60(2):436-442. (Targeting Trends 11q2)

Ritter S, Li AJ, Wang Q, Dinh TT. (2011) Minireview: The value of looking backward: the essential role of the hindbrain in counterregulatory responses to glucose deficit. Endocrinology 152(11):4019-4032. (Targeting Trends 12q1)

Taxini CL, Takakura AC, Gargaglioni LH, Moreira TS. (2011) Control of the central chemoreflex by A5 noradrenergic neurons in rats. Neuroscience 199:177-186. (Targeting Trends 12q1)

See also: Society for Neuroscience 2011 Abstracts


Carvalho AF, Reyes AR, Sterling RC, Unterwald E, Van Bockstaele EJ (2010) Contribution of limbic norepinephrine to cannabinoid-induced aversion. Psychopharmacology (Berl) 211(4):479-491. (Targeting Trends 10q4)

Coradazzi M, Gulino R, Garozzo S, Leanza G (2010) Selective Lesion of the Developing Central Noradrenergic System: Short- and Long-Term Effects and Reinnervation by Noradrenergic-Rich Tissue Grafts. J Neurochem 114(3):761-771. (Targeting Trends 10q3)

Emanuel AJ, Ritter S (2010) Hindbrain Catecholamine Neurons Modulate the Growth Hormone But Not the Feeding Response to Ghrelin. Endocrinology 151(7):3237-3246. (Targeting Trends 10q3)

Gompf HS, Mathai C, Fuller PM, Wood DA, Pedersen NP, Saper CB, Lu J (2010) Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment. J Neurosci 30(43):14543-14551. (Targeting Trends 11q1)

Itoi K, Sugimoto N (2010) The brainstem noradrenergic systems in stress, anxiety, and depression. J Neuroendocrinol 22(5):355-361. (Targeting Trends 10q2)

Marques-Lopes J, Pinho D, Albino-Teixeira A, Tavares I (2010) The hyperalgesic effects induced by the injection of angiotensin II into the caudal ventrolateral medulla are mediated by the pontine A(5) noradrenergic cell group. Brain Res 1325:41-52. (Targeting Trends 10q2)

Milstein JA, Dalley JW, Robbins TW (2010) Methylphenidate-induced impulsivity: pharmacological antagonism by beta-adrenoreceptor blockade. J Psychopharmacol 24:309-321. (Targeting Trends 10q2)

Northrop LE, Polston EK, Erskine MS (2010) Noradrenergic Nuclei that Receive Sensory Input During Mating and Project to the Ventromedial Hypothalamus Play a Role in Mating-Induced Pseudopregnancy in the Female Rat. J Neuroendocrinol 22(10):1061-1071. (Targeting Trends 10q4)

Potes CS, Turek VF, Cole RL, Vu C, Roland BL, Roth JD, Riediger T, Lutz TA (2010) Noradrenergic neurons of the area postrema mediate amylin’s hypophagic action. Am J Physiol Regul Integr Comp Physiol 299(2):R623-631. (Targeting Trends 10q4)

Vianna DM, Carrive P (2010) Cardiovascular and behavioural responses to conditioned fear and restraint are not affected by retrograde lesions of A5 and C1 bulbospinal neurons. Neuroscience 166:1210-1218. (Targeting Trends 10q2)

Worlicek M, Knebel K, Linde HJ, Moleda L, Scholmerich J, Straub RH, Wiest R (2010) Splanchnic sympathectomy prevents translocation and spreading of E coli but not S aureus in liver cirrhosis. Gut 59(8):1127-1134. (Targeting Trends 10q3)

See also: Society for Neuroscience 2010 Abstracts


Abbott SB, Stornetta RL, Fortuna MG, Depuy SD, West GH, Harris TE, Guyenet PG (2009) Photostimulation of retrotrapezoid nucleus phox2b-expressing neurons in vivo produces long-lasting activation of breathing in rats. J Neurosci 29:5806-5819. (Targeting Trends 09q3)

Brightwell JJ, Taylor BK (2009) Noradrenergic Neurons in the Locus Coeruleus Contribute to Neuropathic Pain. Neuroscience 160:174-185. (Targeting Trends 09q2)

Jinks SL, Carstens E, Antognini JF (2009) Nitrous oxide-induced analgesia does not influence nitrous oxide’s immobilizing requirements. Anesth Analg 109:1111-1116. (Targeting Trends 10q1)

Khan AM, Rapp KL, Ponzio TA, Sanchez-Watts G, Watts AG. (2009) Deletion of Catecholaminergic Neurons by Anti-DBH-Saporin Disrupts Hypothalamic MAP Kinase and CREB Activation. Targeting Trends 10(2).

Nattie E, Li A (2009) Central chemoreception is a complex system function that involves multiple brain stem sites. J Appl Physiol 106:1464-1466. (Targeting Trends 09q3)

See also: Society for Neuroscience 2009 Abstracts


Bienkowski MS, Rinaman L (2008) Noradrenergic inputs to the paraventricular hypothalamus contribute to hypothalamic-pituitary-adrenal axis and central Fos activation in rats after acute systemic endotoxin exposure. Neuroscience 156(4):1093-1102. (Targeting Trends 08q4)

Colombari DS, Pedrino GR, Freiria-Oliveira AH, Korim WS, Maurino IC, Cravo SL (2008) Lesions of medullary catecholaminergic neurons increase salt intake in rats. Brain Res Bull 76:572-578. (Targeting Trends 08q4)

Harle P, Pongratz G, Albrecht J, Tarner IH, Straub RH (2008) An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+ cells. Arthritis Rheum 58:2347-2355. (Targeting Trends 10q2)

Li A, Emond L, Nattie E (2008) Brainstem catecholaminergic neurons modulate both respiratory and cardiovascular function. Adv Exp Med Biol 605:371-376. (Targeting Trends 08q2)

McGaughy J, Ross RS, Eichenbaum H (2008) Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting. Neuroscience 153:63-71. (Targeting Trends 09q2)

Pedrino GR, Rosa DA, Korim WS, Cravo SL (2008) Renal sympathoinhibition induced by hypernatremia: Involvement of A1 noradrenergic neurons. Auton Neurosci 142(1-2):55-63. (Targeting Trends 08q4)

Radley JJ. (2008) Noradrenergic Innervation of the Dorsal Medial Prefrontal Cortex Modulates Hypothalamo-Pituitary-Adrenal Responses to Acute Emotional Stress. Targeting Trends 9(3).

Radley JJ, Williams B, Sawchenko PE (2008) Noradrenergic innervation of the dorsal medial prefrontal cortex modulates hypothalamo-pituitary-adrenal responses to acute emotional stress. J Neurosci 28:5806-5816. (Targeting Trends 08q3)

See also: Society for Neuroscience 2008 Abstracts


Blanco-Centurion C, Gerashchenko D, Shiromani PJ (2007) Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. J Neurosci 27:14041-14048. (Targeting Trends 08q1)

Milstein JA, Lehmann O, Theobald DE, Dalley JW, Robbins TW (2007) Selective depletion of cortical noradrenalin by anti-dopamine beta-hydroxylase-saporin impairs attentional function and enhances the effects of guanfacine in the rat. Psychopharmacology (Berl) 190(1):51-63. (Targeting Trends 07q1)

Rinaman L, Dzmura V (2007) Experimental dissociation of neural circuits underlying conditioned avoidance and hypophagic responses to lithium chloride. Am J Physiol Regul Integr Comp Physiol 293(4): R1495-1503. (Targeting Trends 07q4)

Schiltz JC, Sawchenko PE (2007) Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults. J Comp Neurol 502:455-467. (Targeting Trends 07q3)

See also: Society for Neuroscience 2007 Abstracts


Banihashemi L, Rinaman L (2006) Noradrenergic inputs to the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus underlie hypothalamic-pituitary-adrenal axis but not hypophagic or conditioned avoidance responses to systemic yohimbine. J Neurosci 26(44):11442-11453. (Targeting Trends 07q1)

Bugarith K DTT, Li AJ, Speth RC, Ritter S. (2006) Basomedial Hypothalamic Injections of Neuropeptide Y Conjugated to Saporin Selectively Disrupt Hypothalamic Controls of Food Intake. Targeting Trends 7(4).

Dinh TT, Flynn FW, Ritter S (2006) Hypotensive hypovolemia and hypoglycemia activate different hindbrain catecholamine neurons with projections to the hypothalamus. Am J Physiol Regul Integr Comp Physiol 291(4):R870-R879. (Targeting Trends 06q3)

Fraley GS (2006) Immunolesions of glucoresponsive projections to the arcuate nucleus alter glucoprivic-induced alterations in food intake, luteinizing hormone secretion, and GALP mRNA, but not sex behavior in adult male rats. Neuroendocrinology 83(2):97-105. (Targeting Trends 06q4)

Li A, Nattie E (2006) Catecholamine neurones in rats modulate sleep, breathing, central chemoreception and breathing variability. J Physiol 570(Pt 2):385-396. (Targeting Trends 06q2)

Li AJ, Wang Q, Ritter S (2006) Differential responsiveness of dopamine-beta-hydroxylase gene expression to glucoprivation in different catecholamine cell groups. Endocrinology 147(7):3428-3434. (Targeting Trends 06q3)

Madden CJ, Stocker SD, Sved AF (2006) Attenuation of homeostatic responses to hypotension and glucoprivation after destruction of catecholaminergic rostral ventrolateral medulla (RVLM) neurons. Am J Physiol Regul Integr Comp Physiol 291(3):R751-R759. (Targeting Trends 06q3)

Pedrino GR, Maurino I, de Almeida Colombari DS, Cravo SL (2006) Role of catecholaminergic neurons of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats. Exp. Physiol 91(6):995-1005. (Targeting Trends 07q1)

Ritter S, Dinh TT, Li AJ (2006) Hindbrain catecholamine neurons control multiple glucoregulatory responses. Physiol Behav 89(4):490-500. (Targeting Trends 06q4)

Wiley RG. (2006) Targeted Toxins in Pain. Targeting Trends 7(2).

See also: Society for Neuroscience 2006 Abstracts


Castle M, Comoli E, Loewy AD (2005) Autonomic brainstem nuclei are linked to the hippocampus. Neuroscience 134(2):657-669. (Targeting Trends 05q4)

Dudkin KN, Chueva V, Makarov FN, Bich TG, Roer AE (2005) Impairments in working memory and decision-taking processes in monkeys in a model of Alzheimer’s disease. Neurosci Behav Physiol 35(3):281-289.

Harle P, Mobius D, Carr DJ, Scholmerich J, Straub RH (2005) An opposing time-dependent immune-modulating effect of the sympathetic nervous system conferred by altering the cytokine profile in the local lymph nodes and spleen of mice with type II collagen-induced arthritis. Arthritis Rheum 52:1305-1313. (Targeting Trends 10q2)

Lappi DA (2005) Targeted Toxins from Here to There. Targeting Trends 6(3):1, 6.

Northrop LE, Cameron N, Erskine M. (2005) Noradrenergic inputs to the medial amygdala originate in the A1 and A2 cells groups and release norepinephrine after mating stimulation sufficient to induce pseudopregnancy. Targeting Trends 6(2).

See also: Society for Neuroscience 2005 Abstracts


Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ (2004) Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone. Eur J Neurosci 19(10):2741-2752. (Targeting Trends 04q3)

Cameron NM, Carey P, Erskine MS (2004) Medullary noradrenergic neurons release norepinephrine in the medial amygdala in females in response to mating stimulation sufficient for pseudopregnancy. Brain Res 1022(1-2):137-147. (Targeting Trends 05q1)

Estacio MA, Tsukamura H, Reyes BA, Uenoyama Y, I’anson H, Maeda K (2004) Involvement of brainstem catecholaminergic inputs to the hypothalamic paraventricular nucleus in estrogen receptor alpha expression in this nucleus during different stress conditions in female rats. Endocrinology 145(11):4917-4926. (Targeting Trends 05q1)

Hudson B, Ritter S (2004) Hindbrain catecholamine neurons mediate consummatory responses to glucoprivation. Physiol Behav 82(2-3):241-250. (Targeting Trends 04q4)

Li AJ, Ritter S (2004) Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus. Eur J Neurosci 19(8):2147-2154. (Targeting Trends 04q3)

See also: Society for Neuroscience 2004 Abstracts


Fraley GS, Ritter S (2003) Immunolesion of norepinephrine and epinephrine afferents to medial hypothalamus alters basal and 2-deoxy-D-glucose-induced neuropeptide Y and agouti gene-related protein messenger ribonucleic acid expression in the arcuate nucleus. Endocrinology 144(1):75-83. (Targeting Trends 03q2)

I’Anson H, Sundling LA, Roland SM, Ritter S (2003) Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats. Endocrinology 144(10):4325-4331. (Targeting Trends 04q1)

Jasmin L, Boudah A, Ohara PT (2003) Long-term effects of decreased noradrenergic central nervous system innervation on pain behavior and opioid antinociception. J Comp Neurol 460(1):38-55. (Targeting Trends 03q3)

Madden CJ, Sved AF (2003) Rostral ventrolateral medulla C1 neurons and cardiovascular regulation. Cell Mol Neurobiol 23(4-5):739-749. (Targeting Trends 04q1)

Rinaman L (2003) Hindbrain noradrenergic lesions attenuate anorexia and alter central cFos expression in rats after gastric viscerosensory stimulation. J Neurosci 23(31):10084-10092. (Targeting Trends 04q1)

Ritter S, Watts AG, Dinh TT, Sanchez-Watts G, Pedrow C (2003) Immunotoxin lesion of hypothalamically projecting norepinephrine and epinephrine neurons differentially affects circadian and stressor-stimulated corticosterone secretion. Endocrinology 144(4):1357-1367. (Targeting Trends 03q3)

See also: Society for Neuroscience 2003 Abstracts


Bitner RS, Nikkel AL (2002) Alpha-7 nicotinic receptor expression by two distinct cell types in the dorsal raphe nucleus and locus coeruleus of rat. Brain Res 938:45-54. (Targeting Trends 02q3)

Blanco-Centurion C. (2002) HCRT-SAP Lesion Produces Sleepiness While anti-DBH-SAP Lesion Does Not. Targeting Trends 3(2).

Fraley GS, Dinh TT, Ritter S (2002) Immunotoxic catecholamine lesions attenuate 2DG-induced increase of AGRP mRNA. Peptides 23(6):1093-1099. (Targeting Trends 02q4)

Kingery WS, Agashe GS, Guo TZ, Sawamura S, Davies MF, Clark JD, Kobilka BK, Maze M (2002) Isoflurane and nociception: Spinal alpha2A adrenoceptors mediate antinociception while supraspinal alpha1 adrenoceptors mediate pronociception. Anesthesiol 96:367-374. (Targeting Trends 02q2)

Li X, Conklin D, Ma W, Zhu X, Eisenach JC (2002) Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain. Pain 97:117-125. (Targeting Trends 02q4)

See also: Forum of European Neuroscience 2002 Abstracts and Society for Neuroscience 2002 Abstracts


Daniels D, Miselis RR, Flanagan-Cato LM (2001) Transneuronal Tracing from Sympathectomized Lumbar Epaxial Muscle in Female Rats. J Neurobiol 48(4):278-290. (Targeting Trends 01q4)

Demas GE, Bartness TJ (2001) Novel method for localized, functional sympathetic nervous system denervation of peripheral tissue using guanethidine. J Neurosci Meth 112:21-28. (Targeting Trends 02q1)

Deuchars J, Deuchars S (2001) It’s enough to raise your blood pressure! Trends Neurosci 24(4):200. (Targeting Trends 01q4)

Jasmin L, Ohara PT (2001) Long-term intrathecal catheterization in the rat. J Neurosci Meth 110:81-89. (Targeting Trends 02q1)

Ritter S, Bugarith K, Dinh TT (2001) Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation. J Comp Neurol 432(2):197-216. (Targeting Trends 01q3)

Schreihofer A. (2001) Immunolesioning – From Spinal Cord to Brain. Targeting Trends 2(1).

Vogt LJ, Sim-Selley LJ, Childers SR, Wiley RG, and Vogt BA (2001) Colocalization of m-opioid receptors and activated G-proteins in rat cingulate cortex. J Pharmacol Exper Ther 299:840-848. (Targeting Trends 02q1)

See also: Society for Neuroscience 2001 Abstracts


Sawamura S, Kingery WS, Davies MF, Agashe GS, Clark JD, Kobilka BK, Hashimoto T, Maze M (2000) Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of a2B adrenoceptors. J Neurosci 20(24):9242-9251. (Targeting Trends 01q2)

Schreihofer AM, Guyenet PG (2000) Sympathetic reflexes after depletion of bulbospinal catecholaminergic neurons with anti-DBH-saporin. Am J Physiol Regul Integr Comp Physiol 279:R729-R742.

Schreihofer AM, Guyenet PG (2000) Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats. Am J Physiol Regul Integr Comp Physiol 279:R1753-R1762.

Schreihofer AM, Stornetta RL, Guyenet PG (2000) Regulation of sympathetic tone and arterial pressure by rostral ventrolateral medulla after depletion of C1 cells in rat. J Physiol 529(1):221-236. (Targeting Trends 01q2)

Schroeter S, Apparsundaram S, Wiley RG, Miner LH, Sesack SR, Blakely RD (2000) Immunolocalization of the cocaine- and antidepressant-sensitive 1-norepinephrine transporter. J Comp Neurol 420:211-232. (Targeting Trends 00q4)

Taylor BK, Roderick RE, Basbaum AI (2000) Brainstem noradrenergic control of nociception is abnormal in the spontaneously hypertensive rat. Neurosci Lett 291:139-142. (Targeting Trends 01q1)

Wiley RG, Kline IV RH (2000) Neuronal lesioning with axonally transported toxins. J Neurosci Meth 103:73-82. (Targeting Trends 01q2)

See also: Society for Neuroscience 2000 Abstracts


Madden CJ, Ito S, Rinaman L, Wiley RG, Sved AF (1999) Lesions of the C1 catecholaminergic neurons of the ventrolateral medulla in rats using anti-DBH-saporin. Am J Physiol 46:R1063-R1075.

Martin WJ, Gupta NK, Loo CM, Rohde DS, Basbaum AI (1999) Differential effects of neurotoxic destruction of descending noradrenergic pathways on acute and persistent nociceptive processing. Pain 80:57-65. doi: 10.1016/s0304-3959(98)00194-8

Summary: The authors used Anti-DBH-SAP to re-examine the contribution of noradrenergic pathways to nociception and to morphine analgesia. They also evaluated morphine analgesia in the formalin test and found that toxin-treated animals exhibited enhanced morphine analgesia. These results establish the utility of using this immunotoxin to selectively destroy subpopulations of noradrenergic cell groups and provide evidence that acute and persistent nociception are differentially regulated by descending noradrenergic pathways.
Dose: Intrathecal treatment with Anti-DBH-SAP attenuates formalin pain (5.0 µg/20 µl).


Blessing WW, Lappi DA, Wiley RG (1998) Destruction of locus coeruleus neuronal perikarya after injection of anti-dopamine-beta-hydroxylase immunotoxin into the olfactory bulb of the rat. Neurosci Lett 243:85-88.

Rohde DS, Basbaum AI (1998) Activation of coeruleospinal noradrenergic inhibitory controls during withdrawal from morphine in the rat. J Neurosci 18(11):4393-4402.


Picklo MJ (1997) Methods of sympathetic degeneration and alteration. J Auton Nerv Syst 62:111-125.


Wrenn CC, Picklo MJ, Lappi DA, Robertson D, Wiley RG (1996) Lesioning of medullary noradrenergic and adrenergic neurons using the immunotoxin anti-DBH-saporin. Soc Neurosci Mtg, Washington DC, Abstract.

Wrenn CC, Picklo MJ, Lappi DA, Robertson DR, Wiley RG (1996) Central noradrenergic lesioning using anti-DBH-saporin: anatomical findings. Brain Res 740:175-186.


Picklo MJ, Wiley RG, Lonce S, Lappi DA, Robertson D (1995) Anti-dopamine beta hydroxylase immunotoxin induced sympathectomy in adult rats. J Pharmacol Exp Therap 275:1003-1010.


Picklo MJ, Wiley RG, Lappi DA, Robertson D (1994) Noradrenergic lesioning with an anti-dopamine beta-hydroxylase immunotoxin. Brain Res 666:195-200.


Picklo MJ, Lappi DA, Wiley RG, Robertson D (1993) Noradrenergic lesioning using anti-DBH immunotoxin. Soc Neurosci Mtg, Washington DC, Abstract #19-10.


Lewis EJ, Asnani LP (1992) Soluble and membrane-bound forms of dopamine b-hydroxylase are encoded by the same mRNA. J Biol Chem 267:494-500.