Author:
Davis Adeola R.,Shields Angela D.,Brigman Jonathan L.,Norcross Maxine,McElligott Zoe A.,Holmes Andrew,Winder Danny G.
Abstract
Extinction, a form of learning that has the ability to reshape learned behavior based on new experiences, has been heavily studied utilizing fear learning paradigms. Mechanisms underlying extinction of positive-valence associations, such as drug self-administration and place preference, are poorly understood yet may have important relevance to addiction treatment. Data suggest a major role for the noradrenergic system in extinction of fear-based learning. Employing both pharmacological and genetic approaches, we investigated the role of the α2-adrenergic receptor (α2-AR) in extinction of cocaine-conditioned place preference (CPP) and glutamatergic transmission in the bed nucleus of the stria terminalis (BNST). We found that pre-extinction systemic treatment with the α2-AR antagonist yohimbine impaired cocaine CPP extinction in C57BL/6J mice, an effect that was not mimicked by the more selective α2-AR antagonist, atipamezole. Moreover, α2A-AR knockout mice exhibited similar cocaine CPP extinction and exacerbated extinction impairing effects of yohimbine. Using acute brain slices and electrophysiological approaches, we found that yohimbine produces a slowly evolving depression of glutamatergic transmission in the BNST that was not mimicked by atipamezole. Further, this action was extant in slices from α2A-AR knockout mice. Our data strongly suggest that extinction-modifying effects of yohimbine are unlikely to be due to actions at α2A-ARs.
Publisher
Cold Spring Harbor Laboratory
Subject
Cellular and Molecular Neuroscience,Cognitive Neuroscience,Neuropsychology and Physiological Psychology
Cited by
34 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献