1. Mesolimbic neuropeptide W coordinates stress responses under novel environments.
- Author
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Motoike T, Long JM, Tanaka H, Sinton CM, Skach A, Williams SC, Hammer RE, Sakurai T, and Yanagisawa M
- Subjects
- Animals, Central Amygdaloid Nucleus pathology, Dopaminergic Neurons pathology, Mice, Mice, Knockout, Neuropeptides genetics, Pain genetics, Pain pathology, Rats, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Receptors, Neuropeptide genetics, Receptors, Neuropeptide metabolism, Tyrosine 3-Monooxygenase genetics, Tyrosine 3-Monooxygenase metabolism, Avoidance Learning, Behavior, Animal, Central Amygdaloid Nucleus metabolism, Dopaminergic Neurons metabolism, Neuropeptides metabolism, Pain metabolism
- 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.
- Published
- 2016
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