Premium
Central amygdala relaxin‐3/relaxin family peptide receptor 3 signalling modulates alcohol seeking in rats
Author(s) -
Walker Leigh C,
Kastman Hanna E,
Krstew Elena V,
Gundlach Andrew L,
Lawrence Andrew J
Publication year - 2017
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13955
Subject(s) - yohimbine , anxiogenic , central nucleus of the amygdala , extended amygdala , stria terminalis , endocrinology , medicine , amygdala , neuropeptide , receptor , pharmacology , antagonist , anxiolytic
Background and Purpose Alcohol use disorders are a leading cause of preventable deaths worldwide, and stress is a major trigger of relapse. The neuropeptide relaxin‐3 and its cognate receptor, relaxin family peptide receptor 3 (RXFP3), modulate stress‐induced relapse to alcohol seeking in rats, and while the bed nucleus of the stria terminalis has been implicated in this regard, the central nucleus of the amygdala (CeA) also receives a relaxin‐3 innervation and CeA neurons densely express RXFP3 mRNA. Moreover, the CeA is consistently implicated in both stress and addictive disorders. Yohimbine precipitates relapse‐like behaviour in rodents, although exactly how yohimbine induces relapse is unknown, possibly by increasing stress levels and inducing heightened cue reactivity. Experimental Approach In the current study, we examined the effects of yohimbine (1 mg·kg −1 , i.p.) on anxiety‐like behaviour in alcohol‐experienced rats. Furthermore, we assessed CeA neuronal activation following yohimbine‐induced reinstatement of alcohol seeking and the role of the relaxin‐3/RXFP3 signalling within the CeA in yohimbine‐induced reinstatement to alcohol seeking. Key Results Low‐dose yohimbine was anxiogenic in rats with a history of alcohol use. Furthermore, yohimbine‐induced reinstatement of alcohol seeking increased Fos activation in CeA corticotrophin‐releasing factor, dynorphin and GABA neurons compared with naïve and vehicle controls. Bilateral intra‐CeA injections of the selective RXFP3 antagonist, R3(B1‐22)R, attenuated yohimbine‐induced reinstatement of alcohol seeking. Conclusions Collectively, these data suggest that the CeA is a node where yohimbine acts to induce reinstatement of alcohol seeking and implicate the relaxin‐3/RXFP3 system within the CeA in this process.