Anti-SERT-SAP References

Anti-SERT-SAP (Cat. #IT-23)

25 entries found for : it-23

Using loss- and gain-of-function approaches to target amygdala-projecting serotonergic neurons in the dorsal raphe nucleus that enhance anxiety-related and conditioned fear behaviors.

Bernabe CS, Caliman IF, Truitt WA, Molosh AI, Lowry CA, Hay-Schmidt A, Shekhar A, Johnson PL (2020) Using loss- and gain-of-function approaches to target amygdala-projecting serotonergic neurons in the dorsal raphe nucleus that enhance anxiety-related and conditioned fear behaviors. J Psychopharmacol 34(4):400-411. doi: 10.1177/0269881119900981

Objective: To investigate the role of amygdala-projecting 5-HT neurons in the DR in innate anxiety and conditioned fear behaviors.

Summary: The studies support the hypothesis that amygdala-projecting 5-HT neurons in the DR represent an anxiety and fear-on network.

Usage: Each rat received two bilateral microinjections per site (100 nL each, 1 μM in artificial cerebrospinal fluid) of either Anti-SERT-SAP or the control Mouse IgG-SAP.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)

S38. Dissecting the functional heterogeneity of serotonergic systems that regulate fear and panic.

Bernabe C, Caliman I, de Abreu A, Dustrude E, Molosh A, Shekhar A, Johnson P (2019) S38. Dissecting the functional heterogeneity of serotonergic systems that regulate fear and panic. Biol Psychiatry 85(10):S311. doi: 10.1016/j.biopsych.2019.03.789

Objective: To elucidate the role of these serotonergic networks on learned fear and innate panic responses.

Summary: LED excitation or lesioning of PeF projecting 5-HT system respectively attenuated and enhanced panic-associated escape/flight behaviors and cardioexcitation following a 7.5 and 20% CO2 challenge.

Usage: Anti-SERT-SAP was injected into the BLA or PeF to lesion these 5-HT pathways.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Serotonin and motherhood: From molecules to mood.

Pawluski JL, Li M, Lonstein JS (2019) Serotonin and motherhood: From molecules to mood. Front Neuroendocrinol 53:100742. doi: 10.1016/j.yfrne.2019.03.001

Summary: Serotonin may affect how mothers perceive or behaviorally readjust to changes in the sensory cues emitted by their offspring as they age. The DR serotonin-lesioned mothers studied by Holschbach and colleagues (2018) were much less maternally aggressive, which was concomitant with reduced serotonin-immunoreactive fiber density in the anterior hypothalamus, a brain site previously implicated in serotonin's influence on aggressive behaviors in male animals.

See: Holschbach MA et al. Serotonin-specific lesions of the dorsal raphe disrupt maternal aggression and caregiving in postpartum rats. Behav Brain Res 348:53-64, 2018.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Serotonin-specific lesions of the dorsal raphe disrupt maternal aggression and caregiving in postpartum rats.

Holschbach MA, Vitale EM, Lonstein JS (2018) Serotonin-specific lesions of the dorsal raphe disrupt maternal aggression and caregiving in postpartum rats. Behav Brain Res 348:53-64. doi: 10.1016/j.bbr.2018.04.008

Objective: To determine the effects of behavioral modifications associated with early motherhood by permanently disrupting serotonin signaling at one of its primary sources, the dorsal raphe (DR).

Summary: Prepartum serotonin-specific lesions of the DRdm impaired maternal aggression. Larger postpartum DR serotonin lesions affected both aggression and caregiving. DR serotonin lesions did not affect postpartum anxiety.

Usage: 1 μL of 0.1M anti-SERT-SAP or control Mouse IgG-SAP was slowly infused into the DR.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)

Raphe pallidus is not important to central chemoreception in a rat model of Parkinson’s disease.

Oliveira LM, Moreira TS, Takakura AC (2018) Raphe pallidus is not important to central chemoreception in a rat model of Parkinson’s disease. Neuroscience 369:350-362. doi: 10.1016/j.neuroscience.2017.11.038

Objective: To investigate if serotonin-expressing neurons in the Raphe pallidus/parapyramidal region (RPa/PPy) are also involved in the modulation of breathing during central chemoreception activation in a PD animal model.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Saporin (Cat. #PR-01)

Serotoninergic projections to the OFC and BLA modulate reversal learning

Tapp D, McMurray M (2017) Serotoninergic projections to the OFC and BLA modulate reversal learning. Neuroscience 2017 Abstracts 423.01 / TT12. Society for Neuroscience, Washington, DC.

Summary: Behavioral flexibility, the ability to adapt to changing reward contingencies, is a critical aspect of choice behavior. Such ability is disrupted in numerous psychiatric disorders, such as substance abuse disorders, attention deficit disorder, and obsessive- compulsive disorder. The orbitofrontal cortex (OFC) and the basolateral amygdala (BLA) have been implicated as key regulators for this behavior. Additionally, the neurotransmitter serotonin is known to influence behavioral flexibility, and is disrupted in numerous psychiatric disorders. While serotonin and these brain regions have been examined separately, they have yet to be directly linked in this behavioral context. Using a rat model, this study examined such a relationship by selectively leisoning serotoninergic projections to the OFC, BLA, or both regions with a SERT-conjugated Saporin, and assessing behavioral flexibility in a probabilistic spatial reversal-learning task. Preliminary results indicated that the loss of serotonergic projections to either the OFC, BLA, or both impaired behavioral flexibility. Based on these results, we determined that serotonin regulates reversal learning through its action in the OFC and BLA. Therefore, the serotonergic system may serve as a future therapeutic target for diseases in which behavioral flexibility is impaired, and may explain the effectiveness of serotonin modulators in the treatment of these diseases.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Maternal aggression is impaired by prepartum serotonin-specific lesions of the midbrain dorsal raphe.

Vitale EM, Holschbach MA, Lonstein JS (2016) Maternal aggression is impaired by prepartum serotonin-specific lesions of the midbrain dorsal raphe. Neuroscience 2016 Abstracts 338.01 / SS14. Society for Neuroscience, San Diego, CA.

Summary: The postpartum period in laboratory rats and other animals is characterized by increased maternal responsiveness, decreased anxiety, and increased aggression. Pharmacologically manipulating the serotoninergic system during the postpartum period alters all of these behaviors, and our lab recently found that lesioning serotonergic neurons in the dorsal raphe (DR; primary source of forebrain serotonin) after parturition decreases maternal aggression as well as pup licking in laboratory rats. This demonstrates serotonin’s importance for these behaviors during the postpartum period, but no studies have evaluated the function of serotonin during pregnancy, a highly sensitive period when hormones and peptides alter neurochemistry to initiate maternal responsiveness. Given serotonin’s role in hormone and neuropeptide release, DR serotoninergic activity beginning during pregnancy may be particularly important for the onset of postpartum changes in anxiety, maternal responsiveness, and maternal aggression. To test this hypothesis, we destroyed serotonergic cells with a neurotoxin targeting the serotonin transporter (anti-SERT-saporin; Advanced Targeting Systems) infused into the DR on pregnancy day 15. After parturition, we observed subjects’ maternal caregiving behaviors, maternal motivation during retrieval tests, maternal aggression, and anxiety-like behaviors. We found that DR lesions during pregnancy greatly reduced maternal aggression towards an intruder, and that lesioned mothers also showed increased contact with pups immediately after disruption of the nest site during retrieval tests. Preliminary analysis of serotonin fiber innervation in several forebrain regions indicates tremendous reduction in serotonin fiber density in the amygdala and medial prefrontal cortex of lesioned subjects, but much less so in the medial preoptic area (MPOA). These findings demonstrate that prepartum serotonin-specific lesions of the DR affect particular maternal behaviors, especially aggression, and likely do so by reducing serotonergic innervation of the forebrain in a site-specific manner.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

A unique subdivision of serotonergic neurons in the dorsal raphe nucleus projects to the basolateral amygdala complex to enhance fear-conditioned behaviors.

Bernabe CS, Caliman IF, Abreu ARR, Shekhar A, Johnson PL (2016) A unique subdivision of serotonergic neurons in the dorsal raphe nucleus projects to the basolateral amygdala complex to enhance fear-conditioned behaviors. Neuroscience 2016 Abstracts 74.23 / GGG14. Society for Neuroscience, San Diego, CA.

Summary: The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including fear and anxiety. Previous studies have shown that increased serotonin release in the BLC enhances fear conditioned behaviors, and we recently demonstrated that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7,DHT) injections disrupted fear conditioned behaviors. In 2005 Abrams and colleagues determined that there were robust BLC projections that originate from the midline dorsal (DRD) and ventral (DRV) subdivisions of the dorsal raphe nucleus (DRN), but it was not determined that they were serotonergic. Here we injected a saporin (SAP) toxin coupled to a serotonin transporter (SERT) into the BLC to selectively lesion local serotonergic fibers which replicated disrupted fear conditioning behaviors that was observed in the BLC 5,7DHT study. Since the SERT-SAP can retrogradely lesion the associated cell bodies (Shen et al., 2007) via fast retrograde microtubule associated transport, we also injected the retrograde tracer cholera toxin B (CtB) into the BLC via same the cannula that SERT-SAP was injected. This was done to not only verify loss of serotonergic neurons in DRN subdivisions, but also to specifically verify BLC projecting serotonergic neurons. We later used immunohistochemistry (IHC) to detect SERT in the BLC and observed a 90% decrease in local SERT-immunoreactive fibers. We also verified that almost all CtB-immunoreactive BLC projecting neurons in DRN were also positive for tryptophan hydroxylase (TPH: a serotonergic specific enzyme). We further determined that BLC projecting neurons immunoreactive for both CtB and TPH were primarily located within the midline DRD and DRV divisions of the DRN, and not in the lateral wing (DRVL) divisions of DRN. Regardless of location, the SERT-SAP group had 72% to 74% less CtB/TPH-double immunoreactive neurons than control-SAP group. These data elucidate the roles of serotonergic networks in the pathophysiology of fear, and especially focus on the origins of these pathways as a way to identify potential novel therapeutic targets.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Postpartum lesions targeting serotonergic neurons in the dorsal raphe alter various aspects of maternal behavior

Holschbach MA, Vitale EM, Lonstein JS (2015) Postpartum lesions targeting serotonergic neurons in the dorsal raphe alter various aspects of maternal behavior. Neuroscience 2015 Abstracts 247.17/R3. Society for Neuroscience, Chicago IL.

Summary: The survival and wellbeing of mothers and their young require high levels of maternal care, aggression toward conspecifics, and low anxiety. These behaviors are affected by pharmacological manipulation of serotonin signaling, but no experiments have analyzed in detail the effects of serotonin-specific lesions of the midbrain on all of these postpartum behaviors. We performed serotonin-specific lesions of the dorsal raphe using a saporin-conjugated toxin targeting the serotonin transporter. After dorsal raphe infusion of the toxin or an inactive control conjugate on postpartum day 2, undisturbed maternal behavior was observed daily and retrieval of scattered pups observed every other day for one week after surgery. Anxiety-like behavior was measured in an elevated plus maze and light dark box on postpartum days 8 and 9, respectively, followed by tests of aggression toward a male intruder in the home cage. Serotonergic lesions of the dorsal raphe altered numerous postpartum behaviors. During undisturbed observations, lesioned animals groomed themselves less and showed more crouching over and less licking of pups. Lesions did not greatly affect pup retrieval or anxiety-like behavior, but did reduce the average duration of attack bouts during aggression testing. This experiment indicates new roles for DR serotonin in the suite of behavioral changes occurring during the postpartum period.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Recent progress in research on ribosome inactivating proteins.

Ng TB, Wong JH, Wang H (2009) Recent progress in research on ribosome inactivating proteins. Curr Protein Pept Sci 1323:94-108. doi: 10.2174/138920310790274662

Summary: This review discusses recent literature on ribosome inactivating proteins including the use of saporin-based conjugates in neuroscience and cancer research. Brief descriptions of research done using 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02), dermorphin-SAP (Cat. #IT-12), anti-SERT-SAP (Cat. #IT-23), SSP-SAP (Cat. #IT-11), anti-DBH-SAP (Cat. #IT-03), CTB-SAP (Cat. #IT-14), and other conjugates are provided along with basic information about ribosome inactivating proteins.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02), Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Anti-SERT-SAP (Cat. #IT-23), SSP-SAP (Cat. #IT-11), Anti-DBH-SAP (Cat. #IT-03), CTB-SAP (Cat. #IT-14)

Analysis of inhibitory phase of formalin test: Effects of specific neural lesions

Wiley RG, Moore SA, Kline IV RH (2008) Analysis of inhibitory phase of formalin test: Effects of specific neural lesions. Neuroscience 2008 Abstracts 772.4/MM19. Society for Neuroscience, Washington, DC.

Summary: The formalin test has been widely used as a model of persistent pain. The 90 mins of formalin-induced nocifensive responding can be divided into two phases (phase 1, first ~10 mins; phase 2, last ~60 mins) separated by a period of reduced responding (interphase, IP), that has received relatively little attention. Behavioral inhibition during the IP of the formalin test has been associated with electrophysiological evidence of inhibition of dorsal horn nociceptive neurons (Henry et al, Pain, 82:57, 1999), probably due, at least in part, to local spinal mechanisms. Behavioral inhibition during IP has been shown to be enhanced by morphine and suppressed by naloxone. In the present study, we sought to determine the effect of selective depletion of specific dorsal horn interneurons known to be involved in nociception, i.e. neurons expressing NPY1R, GalR1 or MOR, or selective destruction of cerebral noradrenergic neurons or spinal cord projecting 5-HT neurons on formalin-induced nociceptive behavior, with particular attention to IP. Type-selective lesions were produced by lumbar intrathecal injection of NPY-saporin, galanin-saporin or dermorphin-saporin, respectively. Cerebral noradrenergic neurons and spinally projecting 5-HT neurons were destroyed using the immunotoxins, antiDBH-saporin (intracerebroventricular) or antiSERT-saporin (lumbar intrathecal), respectively. Partial loss of dorsal horn interneurons expressing NPY1R or GalR1 decreased nocifensive responding during IP and phase 2 of the formalin test, while partial loss of MOR-expressing dorsal horn interneurons increased nocifensive responding during IP and during phase 2. Both antiDBH-sap and antiSERT-sap decreased responding during IP, without effects on either phase 1 or 2. These results suggest that the apparent anti-nociception during IP and phase 2 produced by loss of NPY1R- and GalR1-expressing dorsal horn neurons is due to increased inhibition over excitation/facilitation of nociceptive projection neurons, whereas depletion of MOR-expressing interneurons produces the opposite effect. The apparent enhanced nociception during IP, but not phase I and II, produced by antiDBH-sap and antiSERT-sap suggests that these neural systems serve to enhance the excitability of nociceptive projection neurons during the formalin IP. Electrophysiologic and pharmacologic studies of formalin IP in selectively lesioned animals combined with the above behavioral findings may reveal new insights into endogenous modulation of nocifensive motor responses and/or nociception.

Related Products: NPY-SAP (Cat. #IT-28), Anti-SERT-SAP (Cat. #IT-23), Galanin-SAP (Cat. #IT-34), Anti-DBH-SAP (Cat. #IT-03), Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Intra cisterna magna and Rostral ventromedial medulla injection of anti-Serotonin transporter-Saporinpertussis enhanced somatotopically different c-Fos expression and pain related behaviour in the medullary dorsal horn in rats

Sugiyo S, Uehashi D, Masawaki A, Ohyamaguchi A, Abe T, Yonehara N, Takemura M (2008) Intra cisterna magna and Rostral ventromedial medulla injection of anti-Serotonin transporter-Saporinpertussis enhanced somatotopically different c-Fos expression and pain related behaviour in the medullary dorsal horn in rats. Neuroscience 2008 Abstracts 369.11/KK23. Society for Neuroscience, Washington, DC.

Summary: The rostral ventromedial medulla (RVM) is a key center in descending pain modulator, which contain serotonergic neurons having descending projectional terminals in the trigeminal caudal nucleus (Vc; medullary dorsal horn). The functional significance of serotonergic neurons in the RVM is largely unknown. Pretreatment with anti IgG serotonin transporter conjugated with neurotoxin, saporin (anti-SERT-SAP; Advanced Targeting Systems) selectively eliminates cells bearing serotonin transporter, namely serotonergic neurons. 2-4 weeks after injection of anti-SERT-SAP (0.5 µM, 10 nl) into the RVM, the number of serotonin-immunoreactive (IR) cells in the RVM significantly decreased. Formalin injection (1,25% in saline) into the upper lip induced biphasic nociceptive pain-related behavior (PRB). In the rats anti-SERT-SAP-pretreated into the RVM, showed decreased the number of formalin-induced PRB at 1st and 2nd phase compared with the Blank-SAP-pretreated control. 2-4 weeks after intra cisterna magna (CM) pretreatment of anti-SERT-SAP(5 µM, 5 µl), the number of serotonin-IR cells in the RVM also reduced. In stark contrast to the results of pretreatment into the RVM, anti-SERT-SAP-pretreated rats into the CM increased the number of formalin-induced PRB at 1st and 2nd phase. These results indicate that serotonergic neurons in the RVM are constituted by two groups, 1) having pronociceptive function and 2) antinociceptive function projecting to the superficial layers of the Vc.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Central chemoreception is a complex system function that involves multiple brain stem sites.

Nattie E, Li A (2009) Central chemoreception is a complex system function that involves multiple brain stem sites. J Appl Physiol 106:1464-1466. doi: 10.1152/japplphysiol.00112.2008

Summary: This short review discusses central chemoreception and the different neuronal subtypes that play roles in this process. The use of anti-SERT-SAP (Cat. #IT-23) and anti-DBH-SAP (Cat. #IT-03) is mentioned in the context of how the loss of each of these cell types affects CO2 response in rats.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Anti-DBH-SAP (Cat. #IT-03)

Raphe Magnus Nucleus is involved in ventilatory but not hypothermic response to CO2.

Dias MB, Nucci TB, Margatho LO, Antunes-Rodrigues J, Gargaglioni LH, Branco LG (2007) Raphe Magnus Nucleus is involved in ventilatory but not hypothermic response to CO2. J Appl Physiol 103(5):1780-1788. doi: 10.1152/japplphysiol.00424.2007

Summary: In this work the authors investigated the role that serotonergic neurons in the Raphe Magnus Nucleus (RMg) play in ventilatory and thermal responses to hypercapnia. 0.1 µl of 1 µM anti-SERT-SAP (Cat. #IT-23) was injected into the RMg of rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. Lesioned animals had a decreased ventilatory response to CO2, but hypercapnia-induced hypothermia was not affected. The data indicate that RMg serotonergic neurons contribute to CO2 ventilatory response but not to maintenance of ventilation.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)

Ketanserin-induced baroreflex enhancement in spontaneously hypertensive rats depends on central 5-HT(2A) receptors.

Shen FM, Wang J, Ni CR, Yu JG, Wang WZ, Su DF (2007) Ketanserin-induced baroreflex enhancement in spontaneously hypertensive rats depends on central 5-HT(2A) receptors. Clin Exp Pharmacol Physiol 34:702-707. doi: 10.1111/j.1440-1681.2007.04626.x

Summary: Ketanserin is an anytihypertensive drug that effectively lowers blood pressure, decreases blood pressure variability, and enhances blood pressure response in spontaneously hypertensive rats. Using the fact that ketanserin is a selective 5-HT2A antagonist the authors investigated which of these effects utilized the 5-HT2A receptor. Following a 5 nmol ventricular injection of anti-SERT-SAP (Cat. #IT-23) the blood pressure parameters modified by ketanserin were monitored. The data suggest that the baroreflex sensitivity-enhancing effects of ketanserin use the 5-HT2A pathway, but antihypertensive effects follow a different route.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Effect of the destruction of cells containing the serotonin reuptake transporter on urethrogenital reflexes.

Gravitt K, Marson L (2007) Effect of the destruction of cells containing the serotonin reuptake transporter on urethrogenital reflexes. J Sex Med 4:322-331. doi: 10.1111/j.1743-6109.2007.00436.x

Summary: Using the fact that the urethrogenital (UG) reflex is an autonomic and somatic response, the authors developed a model for ejaculatory-like reflexes. Anti-SERT-SAP (Cat. #IT-23) was bilaterally injected into the ventrolateral medulla of rats. 80 nl of a 1 µM solution removed inhibition of the UG reflex after acute spinal cord transection, while this reflex could not be evoked in control animals. The data suggest that SERT-expressing neurons in the ventral medulla are involved with the inhibition of UG reflex.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Neurotoxic lesions of serotonin cells in the dorsal raphe reduce compulsive-like nest building in mice

Greene DM, Castillo MR, Alexander KA, McMahan A, Raap DK, Bult-Ito A (2005) Neurotoxic lesions of serotonin cells in the dorsal raphe reduce compulsive-like nest building in mice. Neuroscience 2005 Abstracts 796.10. Society for Neuroscience, Washington, DC.

Summary: Bi-directional selection for thermoregulatory nest-building behavior in house mice (Mus musculus) has resulted in a 40-fold difference in the amount of cotton used for nest-building between the high and the low selected lines (big and small nest-builders, respectively). The efficacy of serotonin re-uptake inhibitors (SSRIs), especially fluoxetine, for the treatment of obsessive-compulsive disorder (OCD) indicates a serotonergic involvement in the disorder. The repetitive nest-building behavior, characteristic of the big nest-builders, is a compulsive-like behavior that is responsive to SSRI treatment. We investigated the functional involvement of serotonergic pathways in excessive, repetitive nest-building behavior in mice by lesioning serotonergic cells in the dorsal raphe using the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or SERT-saporin (Advanced Targeting Systems). 5,7-DHT lesioned mice had a significant decrease in the number of serotonin-stained cells in the dorsal raphe. No decrease was noted in serotonin staining after lesions performed with the SERT-saporin neurotoxin. Mice with successful 5,7-DHT lesions also significantly decreased compulsive-like nest-building as compared to sham and non-surgery controls. These data taken together with additional findings in these mice support the involvement of serotonin pathways in OCD. This data further supports the big nest-builders as a potentially valuable animal model of compulsive behaviors in humans and a means to more clearly identify neurobiological pathways involved in OCD.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Effect of removal of neurons expressing serotonin reuptake transporter on male sexual reflexes

Gravitt KC, Cai RS, Marson L (2004) Effect of removal of neurons expressing serotonin reuptake transporter on male sexual reflexes. Neuroscience 2004 Abstracts 998.2. Society for Neuroscience, San Diego, CA.

Summary: Ejaculatory reflexes are regulated by spinal circuits that are tonically inhibited or facilitated by specific regions of the brain. Serotonin can facilitate or inhibit sexual responses depending on the site of action and the predominate receptor subtype involved. Sexual function, in particular ejaculation, can be reduced by administration of serotonin reuptake inhibitors (SSRI’s). The urethrogenital (UG) reflex comprises erections, rhythmic contractions of perineal muscles and ejaculation in male rats. We previously demonstrated that a direct pathway from the nucleus paragigantocellularis to the lumbosacral cord is involved in regulating the tonic inhibition of UG reflexes. Neurons in the ventral medulla contain serotonin and removal of serotonin inputs in the spinal cord allow the UG reflex to be exposed. The present study examined the effect of specific lesions of ventral medullary neurons containing the serotonin reuptake transporter (SERT) on sexual reflexes. Anti-SERT-saporin (50-100nl, 1uM) was injected bilaterally into the nPGi of male rats. Ten-fourteen days following surgery, animals were deeply anesthetized and the presence of the UG reflex examined. Urethral stimulation was performed before and after cutting the spinal cord (SCT) and recordings made from the bulbospongiosus muscle. Following the experiment immunocytochemical localization of serotonin was examined. In control rats the UG reflex was not present before SCT. In 50% of males that received anti-SERT-saporin the UG reflex was exposed before SCT. Responses after spinal cord transection were similar in all groups. Rats treated with ant-SERT-saporin showed a significant reduction in the number of serotonin containing neurons and a decrease in the intensity staining in the nPGi, parapyramidal region and medullary raphe. These studies suggest that neurons containing serotonin reuptake transporter systems are involved inhibiting male sexual reflexes.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Neurotoxic lesions of serotonin containing cells of the median raphe nucleus produce constant hippocampal theta rhythm in behaving rats

Sundararaman N, Vertes RP, Perry GW (2004) Neurotoxic lesions of serotonin containing cells of the median raphe nucleus produce constant hippocampal theta rhythm in behaving rats. Neuroscience 2004 Abstracts 196.15. Society for Neuroscience, San Diego, CA.

Summary: The median raphe nucleus (MR) is a major serotonin containing cell group with pronounced projections to the forebrain. The MR exerts strong desynchronizing actions on the EEG activity of the hippocampus. MR stimulation desynchronizes the hippocampal EEG (or blocks theta), and electrolytic MR lesions produce continuous theta. Evidence suggests that desynchronizing actions of MR on the hippocampal EEG are mediated by serotonergic (5-HT) cells of MR. Injections of pharmacological agents into MR that suppress 5-HT MR activity generate theta at short latencies and for long durations. We examined the effects of the selective destruction of 5-HT cells of MR using the 5-HT neurotoxin, anti-SERT-SAP (Advanced Targeting Systems) on the EEG activity of the hippocampus in behaving rats. Under deep sodium pentobarbital anesthesia, rats were chronically prepared with bipolar electrodes, bilaterally in the dorsal hippocampus, a cortical screw for recording the cortical EEG and an indwelling cannula placed 3-4 mm dorsal to MR for the injection of anti-SERT-SAP into MR. Following a 5-7 day period of recovery, hippocampal EEG activity was recorded daily for 7 days as rats freely moved about in a shielded enclose, and then re-assessed under the same conditions following neurotoxic lesions. We found that neurotoxic lesions of MR that resulted in a substantial destruction of 5-HT MR cells (80-90%) produced a continuous theta rhythm in rats; that is, during locomotor behavior as well as during states when theta is normally absent, such as immobility and grooming. For some rats, theta was equivalent during complete immobility and active movement. These results support earlier findings that 5-HT cells of MR are directly involved in the desynchronization of the hippocampal EEG, and indicate that the MR exerts a powerful modulatory influence on the hippocampus.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Medullary serotonergic neurons and adjacent neurons that express neurokinin-1 receptors are both involved in chemoreception in vivo.

Nattie EE, Li A, Richerson GB, Lappi DA (2004) Medullary serotonergic neurons and adjacent neurons that express neurokinin-1 receptors are both involved in chemoreception in vivo. J Physiol 556(1):235-253. doi: 10.1113/jphysiol.2003.059766

Summary: The retrotrapezoid nucleus contains neurokinin-1 receptor (NK-1r)-expressing neurons that are involved in chemoreception. NK-1r-expressing neurons are also present in areas that contain medullary serotonergic neurons. These serotonergic neurons have been shown to be chemosensitive in vitro. With two 100-nl injections of 1 µM SP-SAP (Cat. #IT-07), anti-SERT-SAP (Cat. #IT-23), or both, the authors examined whether both cell populations are involved in chemoreception in vivo in rats. The results support that separate populations of serotonergic and NK-1r-expressing neurons are each involved in chemoreception in vivo.

Related Products: SP-SAP (Cat. #IT-07), Anti-SERT-SAP (Cat. #IT-23), Antibody to Serotonin Transporter (SERT, Cat. #AB-N09)

Serotonergic neurons and development: implications for normal brain function and human disease

Richerson GB, Nattie EE, Deneris ES, Lauder JM (2003) Serotonergic neurons and development: implications for normal brain function and human disease. Neuroscience 2003 Abstracts 329. Society for Neuroscience, New Orleans, LA.

Summary: Symposium. Serotonergic neurons have widely divergent projections to virtually all of the CNS, and are involved in a variety of brain functions. This symposium will focus on how dysfunction of 5-HT neurons during development can influence brain function throughout life. G Richerson will discuss pH chemosensitivity of 5-HT neurons, how this changes during development, and the emerging hypothesis that these neurons induce arousal, a feeling of suffocation and hyperventilation in response to increased CO2. E Nattie has used focal manipulations of the raphe in vivo, including cell specific killing with an antibody to the serotonin transporter conjugated to the toxin saporin, to show that dysfunction of 5-HT neurons may lead to a defect in physiologic regulatory processes that are important during development. E Deneris will discuss mutant mice lacking the Pet-1 ETS gene, in which the majority of CNS 5-HT neurons are missing. 25-30% of Pet-1 nulls die during the first postnatal week, which may result from abnormal respiration. Surviving adults display anxiety-like and aggressive behavior. J Lauder will discuss 5-HT as a differentiation signal in prenatal brain development and as a morphogen in craniofacial development. Effects of prenatal exposure to serotonergic drugs or neurotoxins on postnatal outcome will be described. The speakers will introduce new hypotheses about how dysregulation of 5-HT neurons and 5-HT receptors during development may lead to a variety of brain disorders such as SIDS, migraine, autism, panic attacks and anxiety.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Breathing: Rhythmicity, Plasticity, Chemosensitivity.

Feldman JL, Mitchell GS, Nattie EE (2003) Breathing: Rhythmicity, Plasticity, Chemosensitivity. Annu Rev Neurosci 26:239-266. doi: 10.1146/annurev.neuro.26.041002.131103

Summary: Recent research has indicated that specific areas of the brain exert control over several aspects of breathing, such as rhythm generation, reaction to hypoxia, and regulation of carbon dioxide levels and pH. This review covers many of the latest advances, some of which utilize SP-SAP (Cat. #IT-07) and anti-SERT-SAP (Cat. #IT-23). The use of these targeted toxins allows altered breathing behavior through elimination of very specific cell populations.

Related Products: SP-SAP (Cat. #IT-07), Anti-SERT-SAP (Cat. #IT-23)

Specific killing of rat medullary raphe 5-HT neurons by a serotonin transporter antibody-saporin conjugate reduces the ventilatory response to increased CO2 during sleep and wakefulness.

Nattie EE, Li A, Richerson G, Lappi D (2002) Specific killing of rat medullary raphe 5-HT neurons by a serotonin transporter antibody-saporin conjugate reduces the ventilatory response to increased CO2 during sleep and wakefulness. Neuroscience 2002 Abstracts 221.3. Society for Neuroscience, Orlando, FL.

Summary: CO2 increases the firing rate of medullary raphe 5-HT neurons in vitro (Richerson et al., Respir. Physiol. 129: 175-190, 2001) and focal CO2 dialysis in the medullary raphe increases ventilation in the sleeping rat (Nattie and Li, J. Appl. Physiol. 90: 1247-1257, 2001). To examine in vivo the relative importance of these 5-HT neurons in chemoreception we used an antibody to the external ring of the serotonin tranport protein (SERT)(SFN abstract #814.9, 2001) conjugated to the cell toxin saporin (SAP). Rat medullary raphe neurons (P0) in culture assayed by TPOH immunoreactivity were killed by 10 and 5 nM SERT-SAP with peak effects at 4 and 7 days, respectively. Non-serotonergic neurons were unaffected. In adult rats after measurement of baseline ventilatory values, we placed EEG/EMG electrodes and injected the SERT-SAP conjugate (1 uM) into the medullary raphe (two adjacent 100 nl injections). There was substantial loss of TPOH but not NK1R immunoreactivity measured at 14 days. There was no effect on ventilation during air breathing awake or asleep. Ventilation during 7% CO2 was significantly decreased in sleep (P < 0.001; repeated measures ANOVA) at days 1, 3, 7, and 14 (-13 to -15%; P < 0.05; Tukey post-hoc test) and in wakefulness (P < 0.01; repeated measures ANOVA) at days 1, 3, 7, and 14 (-10 to -16%; P < 0.05; Tukey post-hoc test). Medullary raphe serotonergic neurons in the rat play an important role in the ventilatory response to systemic hypercapnia during sleep and wakefulness.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Targeting serotonin re-uptake transporter (SERT) -expressing cells with a monoclonal antibody to an epitope from the extracellular domain of SERT: Results with a saporin conjugate.

Lappi D, Kohls M, Majer K, Russell B, Blakely R Richerson G (2002) Targeting serotonin re-uptake transporter (SERT) -expressing cells with a monoclonal antibody to an epitope from the extracellular domain of SERT: Results with a saporin conjugate. FENS 2002 Abstracts 049.7. Federation of European Neuroscience Societies, Paris, France.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Antibody to Serotonin Transporter (SERT, Cat. #AB-N09)