control-conjugates

Kaushal R, Taylor B, Jamal A, Zhang L, Ma F, Donahue R, Westlund K (2016) GABA-A receptor activity in the noradrenergic locus coeruleus drives trigeminal neuropathic pain in the rat; contribution of NAα1 receptors in the medial prefrontal cortex. Neuroscience 334:148-159. doi: 10.1016/j.neuroscience.2016.08.005

Summary: The goal of this study was to investigate the role of the locus coeruleus (LC) in a rat orofacial pain model of trigeminal neuropathy induced by chronic constrictive injury of the infraorbital nerve (CCI-ION). Mechanical thresholds to von Frey filaments were tested on whisker pads to evaluate neuropathic pain behavior; pain was indicated by development of mechanical hypersensitivity. Noradrenergic (NA) neurons were lesioned with 5-mcg injections of Anti-DBH-SAP (Cat. #IT-03) into the left lateral ventricle. Mouse-IgG-SAP (Cat. #IT-18) was used as a control. After ablation of NA neurons there was a notable increase in the mechanical threshold compared to control animals. They also targeted coeruleotrigeminal NA neurons by injecting Anti-DBH-SAP into the trigeminal brainstem nuclei bilaterally in one animal and saw similar results. Injecting a GABAA receptor antagonist into the LC after injury had an inhibitory effect on nerve injury induced hypersensitivity. Injection of a NAα1 receptor antagonist, but not a NAα2 receptor antagonist, into the medial prefrontal cortex (mPFC) alleviates mechanical hypersensitivity. They conclude that GABAA-mediated activation of NA neurons during CCI-ION can facilitate hypersensitivity through NAα1 receptors in the mPFC, and that the LC is a chronic pain generator.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Young J (2016) Hunger, thirst, sex, and sleep: How the brain controls our passions. Rowman & Littlefield Publishers.

Summary: The author reviews what has been learned about feeding, “Other clever techniques have confirmed that leptin specifically acts upon NPY-containing neurons to depress feeding. One technique is to infuse the hypothalamus with a form of NPY that is linked to a poisonous molecule called saporin. Neurons that normally contain NPY usually release it into their surroundings and then specifically take it back up into the cell so that it is not wasted. When NPY-containing neurons are tricked into taking up NPY linked to saporin, they die but leave other adjacent neurons completely unaffected. Rats treated in this way become completely insensitive to the feeding-restraining effects of leptin because they lack NPY-containing neurons in the arcuate nucleus.”

Related Products: Blank-SAP (Cat. #IT-21), NPY-SAP (Cat. #IT-28)

See Also:

• Bugarith K et al. Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. Endocrinology 146(3):1179-1191, 2005.

Kumar J, Rajkumar R, Lee L, Dawe G (2016) Nucleus incertus contributes to an anxiogenic effect of buspirone in rats: Involvement of 5-HT1A receptors. Neuropharmacology 110:1-14. doi: 10.1016/j.neuropharm.2016.07.019

Summary: The nucleus incertus (NI) is involved in stress and anxiety responses. The NI is a cluster of GABAergic neurons in the brainstem, and coexpresses CRF, 5-HT1A and D2 receptors. Buspirone is a partial agonist of 5-HT1A receptors, an antagonist of D2 receptors, and activates the NI. Buspirone is an anti-anxiety drug, but preclinical studies showed that it induces anxiety at high doses. To see if the NI is necessary for the anxiogenic effects of high doses of buspirone, rats were bilaterally injected with 86 ng of CRF-SAP (Cat. #IT-13) into the NI. Blank-SAP (Cat. #IT-21) was used as a control. NI lesioning alone had an anxiogenic effect in several anxiety screening tests compared to sham-lesioned rats, which suggests that the NI reduces anxiety physiologically. Lesioning with CRF-SAP reduced the anxiogenic effects of intra-NI injections of buspirone. No significant difference in the anxiety screening tests resulted from injecting quinpiole, a D2 agonist, which suggests that the 5HT1A receptors in the NI are involved in the anxiogenic effects of buspirone.

Related Products: CRF-SAP (Cat. #IT-13), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

Matsuura T, Kawasaki M, Hashimoto H, Yoshimura M, Motojima Y, Saito R, Ueno H, Maruyama T, Ishikura T, Sabanai K, Mori T, Ohnishi H, Onaka T, Sakai A, Ueta Y (2016) Possible involvement of the rat hypothalamo-neurohypophysial/-spinal oxytocinergic pathways in acute nociceptive responses. J Neuroendocrinol 28(6) doi: 10.1111/jne.12396

Summary: It has been suggested that the amplification of GABAergic neurons in the inhibitory system induces the selective inhibition by Oxytocin (OXT) of excitability in the spinal cord, and the pain transmitted from the periphery to the dorsal horn of the spinal cord by this action may be attenuated at the spinal cord level. Rats were injected IT with Oxytocin-SAP (Cat. #IT-46) dissolved in saline (0.06 μg/μl), Blank-SAP (Cat. #IT-21) dissolved in saline (0.06 μg/μl), or saline. Formalin-induced acute nociception activated OXT-containing cells in both the magnocellular and parvocellular divisions of hypothalamus, and that the parvocellular division remains activated longer than the magnocellular division. Acute nociception-induced activation of the hypothalamo-neurohypophysial system caused elevation of plasma OXT levels. In addition, the OXTergic spinal pathway may be involved in pain modulation via OXTRs in the spinal cord.

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)

Matsuura T, Kawasaki M, Hashimoto H, Yoshimura M, Motojima Y, Saito R, Ueno H, Maruyama T, Sabanai K, Mori T, Ohnishi H, Sakai A, Ueta Y (2016) Effects of central administration of oxytocin-saporin cytotoxin on chronic inflammation and feeding/drinking behaviors in adjuvant arthritic rats. Neurosci Lett 621:104-110. doi: 10.1016/j.neulet.2016.04.010

Summary: In the present study, Oxytocin-SAP, which chemically disrupts oxytocin (OXT signaling was administered centrally and an OXT receptor (OXTR) antagonist administered peripherally to determine whether central and peripheral OXT is involved in chronic inflammation and feeding/drinking behavior in adjuvant arthritis (AA) rats. Rats were injected i.t. with Oxytocin-SAP (Cat. #IT-46) or Blank-SAP (Cat. #IT-21) dissolved in saline (0.06 μg/μl). The results demonstrated that the arthritis index values were significantly enhanced and suppression of food intake was transiently attenuated in Oxytocin-SAP treated rats when AA developed, The arthritis index and food intake did not significantly change in the OXTR antagonist i.p.-injected rats. These results suggest that central oxytocinergic pathways may be involved in anti-inflammation at the spinal level and suppression of feeding behavior at the forebrain-brainstem level in AA rats.

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)

Angioni L, Cocco C, Ferri G, Argiolas A, Melis M, Sanna F (2016) Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats. Horm Behav 83:23-38. doi: 10.1016/j.yhbeh.2016.05.012

Summary: Oxytocin is well known for its hormonal role in lactation and parturition, but also exerts widespread actions in central nervous system. Previous experiments revealed the existence of a correlation between the changes in locomotor activity found in Oxytocin-SAP-treated rats and the extent of the changes in nigral TH and vesicular glutamate transporters immunoreactivity, provide support for a modulatory role of oxytocin on locomotor activity at the level of the substantia nigra. The day after a prior assessment of spontaneous locomotor activity, rats were randomly injected bilaterally with 0.3 μL of Oxytocin-SAP (Cat. #IT-46, 60 ng/μL/site), or with the same amount of Blank-SAP (Cat. #IT-21, 60 ng/μL/site) or with vehicle (0.3 μL/site of PBS, pH 7.4). Whether oxytocin may be considered as a target for controlling motor disturbances, as those occurring in Parkinson’s disease and/or in other motor disturbances related to basal ganglia dysfunctions, remains to be evaluated

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)

Mittelman-Smith M, Krajewski-Hall S, McMullen N, Rance N (2016) Ablation of KNDy neurons results in hypogonadotropic hypogonadism and amplifies the steroid-induced LH surge in female rats. Endocrinology 157:2015-2027. doi: 10.1210/en.2015-1740

Summary: KNDy neurons are a subpopulation of neurons in the infundibular nucleus that coexpress estrogen receptor α, kisspeptin, and neurokinin B (NKB) mRNA. Previous work indicated that altered signaling from KNDy neurons may play a role in the low levels of circulating sex steroids found in hypogonadotropic hypogonadism. Rats received bilateral 10-ng injections of NK3-SAP (Cat. #IT-63) dorsal to the arcuate nucleus. Blank-SAP (Cat. #IT-21) was used as control. In animals with intact ovaries the NK3-SAP lesion resulted in hypogonadotropic hypogonadism. In contrast, the LH surge in lesioned ovariectomized rats was 3-fold higher, demonstrating that KNDy neurons are integral for the control of serum LH levels, estrous cyclicity, and may also have some control over the magnitude of the LH surge.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Fu R, Chen X, Zuo W, Li J, Kang S, Zhou L, Siegel A, Bekker A, Ye J (2016) Ablation of μ opioid receptor-expressing GABA neurons in rostromedial tegmental nucleus increases ethanol consumption and regulates ethanol-related behaviors. Neuropharmacology 107:58-67. doi: 10.1016/j.neuropharm.2016.02.027

Summary: In this work the authors investigated cellular mechanisms underlying the aversive effects of alcohol that limit its intake. Previous work has linked synaptic inhibition of dopamine neurons in the ventral tegmental area to this aversion. Rats conditioned to ingest ethanol received bilateral injections totaling 3 pmol of Dermorphin-SAP (Cat. #IT-12) into the rostromedial tegemental nucleus (RTMg). Blank-SAP (Cat. #IT-21) was used as a control. Lesioned animals displayed significantly increased preference for, and intake of ethanol, while showing no change in the desire for sucrose. The results indicate that mu opioid expressing GABAergic neurons in the RTMg are highly involved in the regulation of ethanol consumption.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)

Li P, Janczewski W, Yackle K, Kam K, Pagliardini S, Krasnow M, Feldman J (2016) The peptidergic control circuit for sighing. Nature 530:293-297. doi: 10.1038/nature16964

Summary: Sighs are often associated with relief or sadness, but rodents sigh spontaneously dozens of times per hour. There are physiological benefits to sighing, including enhancement of gas exchange and preservation of lung integrity. The authors identify a peptidergic sigh control circuit in the retrotrapezoid nucleus/parafacial respiratory group of the mouse brain that projects to the pre-Bötzinger complex. Mice received bilateral 6.2-ng injections of Bombesin-SAP (Cat. #IT-40) into the pre-Bötzinger complex. Blank-SAP (Cat. #IT-21) was used as control. Elimination of the bombesin receptor-expressing neurons or inhibition of neuromedin B receptor-expressing neurons suppressed sighing. Interfering with the activity of both receptors abolished sigh activity while leaving normal breathing intact. The data suggest that overlapping peptidergic pathways are the core of a sigh control circuit.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Hulsey D, Hays S, Khodaparast N, Ruiz A, Das P, Rennaker R, Kilgard M (2016) Reorganization of motor cortex by vagus nerve stimulation requires cholinergic innervation. Brain Stimul 9:174-181. doi: 10.1016/j.brs.2015.12.007

Summary: Recent work has suggested that vagus nerve stimulation (VNS) can enhance neuroplasticity, and coupled with other training can drive motor cortex reorganization. These findings highlight the potential of VNS to support recovery from neurological disease. Pretrained rats received bilateral injections totaling 3.75 μg of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis (NB). Mouse-IgG-SAP (Cat. #IT-18) was used as control. Control animals displayed a substantial increase in proximal limb representation, lesion of the NB prevented this increase. Motor performance was similar between lesion and control groups, indicating that the difference in representation was not due to altered limb function.

Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)