Mesolimbic neuropeptide W coordinates stress responses under novel environments

Toshiyuki Motoike, Jeffrey M. Long, Hirokazu Tanaka, Christopher M. Sinton, Amber Skach, S. Clay Williams, Robert E Hammer, Takeshi Sakurai, Masashi Yanagisawa

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Neuropeptide 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 stressinduced inhibition was attenuated in the CeAL neurons of NPW-/- mice. Moreover, the response of NPW-/- mice to either formalininduced 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.

Original languageEnglish (US)
Pages (from-to)6023-6028
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - May 24 2016


  • Amygdala |fear
  • Dopaminergic
  • Mouse
  • Pain

ASJC Scopus subject areas

  • General


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