1. Neuropeptide S in the basolateral amygdala mediates an adaptive behavioral stress response in a rat model of posttraumatic stress disorder by increasing the expression of BDNF and the neuropeptide YY1 receptor
Joseph Zohar, Aleksander A Mathé, Ella Vainer, Kaplan Zeev, Hagit Cohen Eur Neuropsychopharmacol . 2018 Jan;28(1):159-170. doi: 10.1016/j.euroneuro.2017.11.006.
Neuropeptide S (NPS) is a regulatory peptide that has anxiolytic and arousal-promoting effects in rodents. We used an animal model of posttraumatic stress disorder (PTSD) to assess long-term behavioral effects of a single dose of NPS, microinjected into the basolateral amygdala (BLA) 1h following exposure to predator-scent stress (PSS). To elucidate the molecular mechanism by which NPS attenuates behavioral stress responses, expression levels of neuropeptide Y (NPY), NPY-Y1 receptor (NPY-Y1R), and brain-derived neurotrophic factor (BDNF) were evaluated in the hippocampus. The behavioral and molecular effects of NPS receptor antagonist (NPS-RA), NPY-Y1R antagonist (NPY-Y1RA), or both administered centrally were evaluated in the same manner. Circulating corticosterone levels were measured at different time points following PSS-exposure. Immediate post-exposure treatment with NPS had a marked protective effect; BLA microinfusion of NPS completely abolished the extreme behavioral response to PSS, restored the decreased expression of BDNF and, unexpectedly, PY-Y1R, but didn't affect the decreased expression of NPY. BLA microinfusion of both NPY-Y1RA and NPS-RA together had an additive effect, which completely prevented the anxiolytic effects of NPS in rats exposed to PSS and disrupted the expression of NPY-Y1R in the hippocampus following NPS infusion. It may therefore be hypothesized that NPS acts, directly or indirectly, on both the NPY-Y1R and NPS receptors and that the cross-talk between NPS and NPY-Y1R may be necessary for the anxiolytic effects of NPS post-exposure. The NPS system might thus contribute to a potential endogenous mechanism underlying the shift towards adaptive behavioral response and thereby might be relevant as a pharmacological target for attenuating stress-related sequelae.
2. Neuropeptide S attenuates methamphetamine-induced stereotyped behavior in rats
Hongxia Chen, Shuzhuo Zhang, Xiaoli Wei, Fan Jiang, Lujia Yang, Xing Li, Weixiu Yuan, Kai Yao, Ning Wu, Ru Zhou, Xingyue Gao Biochem Biophys Res Commun . 2020 Jun 18;527(1):98-103. doi: 10.1016/j.bbrc.2020.04.085.
Effective therapies for Methamphetamine (METH) induced stereotyped behavior are still being explored. It is unclear whether Neuropeptide S (NPS) is involved in the mechanism of METH-induced stereotyped behavior. In the contemporary behavioral study, pretreatment with NPS reduces stereotyped circling significantly, but didn't have any impact on the total incidence of stereotypy and stereotyped sniffing and biting induced by METH (10 mg/kg). When METH (10 mg/kg) was administered to rats, the level of NPS in the cerebrospinal fluid was not affected, but pretreatment with NPS reversed METH-induced glutamate release in the hippocampus and striatum. The findings suggest that NPS receptor system is likely to involve in the METH-overdose-induced behaviors.
3. Modulatory effect of long-term treatment with escitalopram and clonazepam on the expression of anxiety-related neuropeptides: neuromedin U, neuropeptide S and their receptors in the rat brain
Artur Pałasz, Marek Krzystanek, Aneta Piwowarczyk-Nowak, John J Worthington, Aniela Grajoszek, Katarzyna Bogus, Iwona Błaszczyk Mol Biol Rep . 2022 Sep;49(9):9041-9049. doi: 10.1007/s11033-022-07578-9.
Background:Newly identified multifunctional peptidergic modulators of stress responses: neuromedin U (NMU) and neuropeptide S (NPS) are involved in the wide spectrum of brain functions. However, there are no reports dealing with potential molecular relationships between the action of diverse anxiolytic or antidepressant drugs and NMU and NPS signaling in the brain. The present work was therefore focused on local expression of the aforementioned stress-related neuropeptides in the rat brain after long-term treatment with escitalopram and clonazepam.Methods:Studies were carried out on adult, male Sprague-Dawley rats that were divided into 3 groups: animals injected with saline (control) and experimental individuals treated with escitalopram (at single dose 5 mg/kg daily), and clonazepam (at single dose 0.5 mg/kg). All individuals were sacrificed under anaesthesia and the whole brain excised. Total mRNA was isolated from homogenized samples of amygdala, hippocampus, hypothalamus, thalamus, cerebellum and brainstem. Real time-PCR method was used for estimation of related NPS, NPS receptor (NPSR), NMU, NMU and receptor 2 (NMUR2) mRNA expression. The whole brains were also sliced for general immunohistochemical assessment of the neuropeptides expression.Results:Chronic administration of clonazepam resulted in an increase of NMU mRNA expression and formation of NMU-expressing fibers in the amygdala, while escitalopram produced a significant decrease in NPSR mRNA level in hypothalamus. Long-term escitalopram administration affects the local expression of examined neuropeptides mRNA in a varied manner depending on the brain structure.Conclusions:Pharmacological effects of escitalopram may be connected with local at least partially NPSR-related alterations in the NPS/NMU/NMUR2 gene expression at the level selected rat brain regions. A novel alternative mode of SSRI action can be therefore cautiously proposed.
