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Chronic alcohol exposure disrupts CB 1 regulation of GABAergic transmission in the rat basolateral amygdala
Author(s) -
Varodayan Florence P.,
Bajo Michal,
Soni Neeraj,
Luu George,
Madamba Samuel G.,
Schweitzer Paul,
Roberto Marisa
Publication year - 2017
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12369
Subject(s) - am251 , basolateral amygdala , chemistry , neurotransmission , gabaergic , endocrinology , medicine , endocannabinoid system , cannabinoid , postsynaptic potential , central nucleus of the amygdala , gabaa receptor , cannabinoid receptor , pharmacology , amygdala , agonist , neuroscience , receptor , biology , biochemistry
The basolateral nucleus of the amygdala (BLA) is critical to the pathophysiology of anxiety‐driven alcohol drinking and relapse. The endogenous cannabinoid/type 1 cannabinoid receptor (eCB/CB 1 ) system curbs BLA‐driven anxiety and stress responses via a retrograde negative feedback system that inhibits neurotransmitter release, and BLA CB 1 activation reduces GABA release and drives anxiogenesis. Additionally, decreased amygdala CB 1 is observed in abstinent alcoholic patients and ethanol withdrawn rats. Here, we investigated the potential disruption of eCB/CB 1 signaling on GABAergic transmission in BLA pyramidal neurons of rats exposed to 2–3 weeks intermittent ethanol. In the naïve rat BLA, the CB 1 agonist WIN 55,212‐2 (WIN) decreased GABA release, and this effect was prevented by the CB 1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium‐dependent activity. This retrograde tonic eCB/CB 1 signaling was diminished in chronic ethanol exposed rats, suggesting a functional impairment of the eCB/CB 1 system. In contrast, acute ethanol increased GABAergic transmission similarly in naïve and chronic ethanol exposed rats, via both presynaptic and postsynaptic mechanisms. Notably, CB 1 activation impaired ethanol's facilitation of GABAergic transmission across both groups, but the AM251‐induced and ethanol‐induced facilitation of GABA release was additive, suggesting independent presynaptic sites of action. Collectively, the present findings highlight a critical CB 1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol‐dependent state.