Mesolimbic neuropeptide W coordinates stress responses under novel environments
Long, Jeffrey M.
Sinton, Christopher M.
Williams, S. Clay
Hammer, Robert E.
AffiliationUniv Arizona, Dept Med, Arizona Resp Ctr
MetadataShow full item record
PublisherNATL ACAD SCIENCES
CitationMesolimbic neuropeptide W coordinates stress responses under novel environments 2016, 113 (21):6023 Proceedings of the National Academy of Sciences
RightsCopyright © 2016 The Authors. Published by National Academy of Sciences.
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AbstractNeuropeptide B (NPB) and neuropeptide W(NPW) are endogenous neuropeptide ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimbic region possess tyrosine hydroxylase immunoreactivity, indicating that a small subset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limbic system nuclei in adult mouse brain: the lateral bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhibition of cellular activity, but this stress-induced inhibition was attenuated in the CeAL neurons of NPW-/- mice. Moreover, the response of NPW-/- mice to either formalin-induced pain stimuli or a live rat (i. e., a potential predator) was abnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the behavior of NPW-/- mice in a habituated environment was indistinguishable from that of wildtype mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments.
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VersionFinal accepted manuscript
SponsorsKeck Foundation; Perot Family Foundation; Exploratory Research for Advanced Technology of Japan Science and Technology Agency; World Premier International Research Center Initiative from the Ministry of Education, Culture, Sports, Science and Technology, Japan; Intramural Research Program of the NIH