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Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala.
Addict Biol. 2017 May; 22(3):766-778.AB

Abstract

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/CB1) system curbs BLA-driven anxiety and stress responses via a retrograde negative feedback system that inhibits neurotransmitter release, and BLA CB1 activation reduces GABA release and drives anxiogenesis. Additionally, decreased amygdala CB1 is observed in abstinent alcoholic patients and ethanol withdrawn rats. Here, we investigated the potential disruption of eCB/CB1 signaling on GABAergic transmission in BLA pyramidal neurons of rats exposed to 2-3 weeks intermittent ethanol. In the naïve rat BLA, the CB1 agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent activity. This retrograde tonic eCB/CB1 signaling was diminished in chronic ethanol exposed rats, suggesting a functional impairment of the eCB/CB1 system. In contrast, acute ethanol increased GABAergic transmission similarly in naïve and chronic ethanol exposed rats, via both presynaptic and postsynaptic mechanisms. Notably, CB1 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 CB1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state.

Authors+Show Affiliations

Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute (TSRI), La Jolla, CA, USA.Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute (TSRI), La Jolla, CA, USA.Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute (TSRI), La Jolla, CA, USA. Faculty of Health and Medical Sciences, University of Copenhagen (UCPH), Denmark.Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute (TSRI), La Jolla, CA, USA.Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute (TSRI), La Jolla, CA, USA.Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute (TSRI), La Jolla, CA, USA.Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute (TSRI), La Jolla, CA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26786379

Citation

Varodayan, Florence P., et al. "Chronic Alcohol Exposure Disrupts CB1 Regulation of GABAergic Transmission in the Rat Basolateral Amygdala." Addiction Biology, vol. 22, no. 3, 2017, pp. 766-778.
Varodayan FP, Bajo M, Soni N, et al. Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala. Addict Biol. 2017;22(3):766-778.
Varodayan, F. P., Bajo, M., Soni, N., Luu, G., Madamba, S. G., Schweitzer, P., & Roberto, M. (2017). Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala. Addiction Biology, 22(3), 766-778. https://doi.org/10.1111/adb.12369
Varodayan FP, et al. Chronic Alcohol Exposure Disrupts CB1 Regulation of GABAergic Transmission in the Rat Basolateral Amygdala. Addict Biol. 2017;22(3):766-778. PubMed PMID: 26786379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala. AU - Varodayan,Florence P, AU - Bajo,Michal, AU - Soni,Neeraj, AU - Luu,George, AU - Madamba,Samuel G, AU - Schweitzer,Paul, AU - Roberto,Marisa, Y1 - 2016/01/20/ PY - 2015/09/18/received PY - 2015/11/18/revised PY - 2015/12/14/accepted PY - 2016/1/21/pubmed PY - 2017/11/3/medline PY - 2016/1/21/entrez KW - Basolateral amygdala KW - GABA KW - endocannabinoid (eCB) KW - ethanol KW - type 1 cannabinoid receptor (CB1) KW - whole cell recordings SP - 766 EP - 778 JF - Addiction biology JO - Addict Biol VL - 22 IS - 3 N2 - 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/CB1) system curbs BLA-driven anxiety and stress responses via a retrograde negative feedback system that inhibits neurotransmitter release, and BLA CB1 activation reduces GABA release and drives anxiogenesis. Additionally, decreased amygdala CB1 is observed in abstinent alcoholic patients and ethanol withdrawn rats. Here, we investigated the potential disruption of eCB/CB1 signaling on GABAergic transmission in BLA pyramidal neurons of rats exposed to 2-3 weeks intermittent ethanol. In the naïve rat BLA, the CB1 agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent activity. This retrograde tonic eCB/CB1 signaling was diminished in chronic ethanol exposed rats, suggesting a functional impairment of the eCB/CB1 system. In contrast, acute ethanol increased GABAergic transmission similarly in naïve and chronic ethanol exposed rats, via both presynaptic and postsynaptic mechanisms. Notably, CB1 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 CB1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state. SN - 1369-1600 UR - https://www.unboundmedicine.com/medline/citation/26786379/Chronic_alcohol_exposure_disrupts_CB1_regulation_of_GABAergic_transmission_in_the_rat_basolateral_amygdala_ L2 - https://doi.org/10.1111/adb.12369 DB - PRIME DP - Unbound Medicine ER -