Disentangling the effects of Corticotrophin Releasing Factor and GABA release from the ventral bed nucleus of the stria terminalis on ethanol self-administration in mice

Abstract

AbstractExcessive alcohol use causes a great deal of harm and negative health outcomes. Corticotrophin releasing factor (CRF), a stress-related neuropeptide, has been implicated in binge ethanol intake and ethanol dependence. CRF containing neurons in the bed nucleus of the stria terminalis (BNSTCRF) can control ethanol consumption. These BNSTCRFneurons also release GABA, raising the question, is it CRF or GABA release or both that is controlling alcohol consumption. Here, we used viral vectors to separate the effects of CRF and GABA release from BNSTCRFneurons on the escalation of ethanol intake in an operant self-administration paradigm in male and female mice. We found that CRF deletion in BNST neurons reduces ethanol intake in both sexes, with a stronger effect in males. For sucrose self-administration there was no effect of CRF deletion. Suppression of GABA release, via knockdown of vGAT, from BNSTCRFproduced a transient increase in ethanol operant self-administration following in male mice, and reduced in motivation to work for sucrose on a progressive ratio schedule of reinforcement in a sex-dependent manner. Together, these results highlight how different signaling molecules from the same populations of neurons can bidirectionally control behavior. Moreover, they suggest that BNST CRF release is important for high intensity ethanol drinking that precedes dependence, whereas GABA release from these neurons may play a role in regulating motivation.