Amygdala arginine vasopressin modulates chronic ethanol withdrawal anxiety-like behavior in the social interaction task.

Abstract

BACKGROUND Chronic ethanol exposure induces neurobehavioral maladaptations in the brain though the precise changes have not been fully explored. The central amygdala (CEA) regulates anxiety-like behavior induced by withdrawal from chronic intermittent ethanol (CIE) exposure and the arginine vasopressin (AVP) system within the CEA regulates many anxiety-like behaviors. Thus, adaptations occur in the CEA AVP system due to chronic ethanol exposure which lead to anxiety-like behaviors in rats. METHODS Chronic exposure to a low dose ethanol (4.5% wt/vol) induces anxiety-like behavior in rats. Wistar or Sprague-Dawley rats were exposed to a modified CIE or CIE while intra-CEA microinjections of AVP or a V1b receptor antagonist were used to elicit or block withdrawal induced anxiety. Additionally, AVP microinjections into the CEA were given 24 hours following 15 days of continuous high dose ethanol (7% wt/vol), a time period when rats no longer express anxiety. Chemogenetics was also used to activate the basolateral amygdala or deactivate the dorsal periaqueductal grey (dm/dlPAG) to elicit or block withdrawal induced anxiety. RESULTS AVP microinjected into the CEA in lieu of exposure to the first two cycles of CIE was sufficient to induce anxiety-like behavior in these commonly used rat strains. The V1b receptor antagonist, but not an oxytocin receptor agonist, into the CEA during the first two withdrawal cycles suppressed anxiety. However, activation of the basolateral amygdala in lieu of exposure to the first two cycles of CIE was insufficient to induce anxiety-like behavior. AVP microinjection into the CEA 24 hours into withdrawal re-elicited anxiety-like behavior and deactivation of the dm/dlPAG reduced this effect of CEA AVP. CONCLUSIONS Taken together, this study demonstrates a role of CEA AVP and a CEA-dm/dlPAG circuit in the development of anxiety induced by CIE. Such information is valuable for identifying novel therapeutic targets for alcohol and anxiety associated disorders. This article is protected by copyright. All rights reserved.