Mesolimbic neuropeptide W coordinates stress responses under novel environments.

Abstract

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 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 wild-type 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.

• Authors: Toshiyuki Motoike, Jeffrey M Long, Hirokazu Tanaka, Christopher M Sinton, Amber Skach, S Clay Williams, Robert E Hammer, Takeshi Sakurai, Masashi Yanagisawa
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 113 Issue 21 Pg. 6023-8 (May 24 2016) ISSN: 1091-6490 [Electronic] United States
• PMID: 27140610 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Neuropeptides
• Npbwr1 protein, mouse
• Receptors, G-Protein-Coupled
• Receptors, Neuropeptide
• neuropeptide W, mouse
• Tyrosine 3-Monooxygenase

Topics

• Animals
• Avoidance Learning
• Behavior, Animal
• Central Amygdaloid Nucleus (metabolism, pathology)
• Dopaminergic Neurons (metabolism, pathology)
• Mice
• Mice, Knockout
• Neuropeptides (genetics, metabolism)
• Pain (genetics, metabolism, pathology)
• Rats
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Receptors, Neuropeptide (genetics, metabolism)
• Tyrosine 3-Monooxygenase (genetics, metabolism)