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Chronic ethanol exposure decreases CB 1 receptor function at GABA ergic synapses in the rat central amygdala
Author(s) -
Varodayan Florence P.,
Soni Neeraj,
Bajo Michal,
Luu George,
Madamba Samuel G.,
Schweitzer Paul,
Parsons Loren H.,
Roberto Marisa
Publication year - 2016
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.12256
Subject(s) - am251 , cannabinoid receptor , gabaergic , chemistry , cannabinoid , inhibitory postsynaptic potential , central nucleus of the amygdala , gabaa receptor , endocannabinoid system , neurotransmission , pharmacology , postsynaptic potential , ethanol , cannabinoid receptor type 2 , medicine , amygdala , agonist , endocrinology , receptor , neuroscience , biology , biochemistry
The endogenous cannabinoids ( eCBs ) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and Type 1 cannabinoid receptor ( CB 1 ) expression and function in brain regions associated with addiction. CB 1 inhibits GABA release, and GABA ergic dysregulation in the central nucleus of the amygdala ( CeA ) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB 1 signaling of rat CeA GABA ergic transmission following intermittent ethanol exposure. In the CeA of alcohol‐naive rats, CB 1 agonist WIN 55,212‐2 ( WIN ) decreased the frequency of spontaneous and miniature GABA A receptor‐mediated inhibitory postsynaptic currents ( s/mIPSCs ). This effect was prevented by CB 1 antagonism, but not Type 2 cannabinoid receptor ( CB 2 ) antagonism. After 2–3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol‐induced impairments in CB 1 function. The CB 1 antagonist AM 251 revealed a tonic eCB / CB 1 control of GABA ergic transmission in the alcohol‐naive CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB 1 influence on mIPSC , but not sIPSC , frequency. Finally, acute ethanol increased CeA GABA release in both naive and ethanol‐exposed rats. Although CB 1 activation prevented this effect, the AM 251‐ and ethanol‐induced GABA release were additive, ruling out a direct participation of CB 1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB 1 influence on CeA GABA ergic transmission and indicate that the CeA is particularly sensitive to alcohol‐induced disruptions of CB 1 signaling.