Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala

Florence P. Varodayan; Michal Bajo; Neeraj Soni; George Luu; Samuel G. Madamba; Paul Schweitzer; Marisa Roberto

doi:10.1111/adb.12369

Chronic alcohol exposure disrupts CB₁ regulation of GABAergic transmission in the rat basolateral amygdala

Florence P. Varodayan, Michal Bajo, Neeraj Soni, George Luu, Samuel G. Madamba, Paul Schweitzer, Marisa Roberto^*

^*Corresponding author for this work

14 Citations (Scopus)

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 Additionally, decreased amygdala CB₁ is observed in abstinent alcoholic patients and ethanol withdrawn rats.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.

Original language	English
Journal	Addiction Biology
Volume	22
Issue number	3
Pages (from-to)	766-778
Number of pages	13
ISSN	1355-6215
DOIs	https://doi.org/10.1111/adb.12369
Publication status	Published - May 2017

Keywords

Basolateral amygdala
endocannabinoid (eCB)
ethanol
GABA
type 1 cannabinoid receptor (CB)
whole cell recordings

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10.1111/adb.12369

http://europepmc.org/articles/pmc4956605?pdf=renderLicence: Other

Cite this

@article{a26669dd7e2d4725a0980a4d1b70d541,

title = "Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala",

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 na{\"i}ve 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 na{\"i}ve 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.",

keywords = "Basolateral amygdala, endocannabinoid (eCB), ethanol, GABA, type 1 cannabinoid receptor (CB), whole cell recordings",

author = "Varodayan, {Florence P.} and Michal Bajo and Neeraj Soni and George Luu and Madamba, {Samuel G.} and Paul Schweitzer and Marisa Roberto",

year = "2017",

month = may,

doi = "10.1111/adb.12369",

language = "English",

volume = "22",

pages = "766--778",

journal = "Addiction Biology",

issn = "1355-6215",

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number = "3",

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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

PY - 2017/5

Y1 - 2017/5

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.

AB - 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.

KW - Basolateral amygdala

KW - endocannabinoid (eCB)

KW - ethanol

KW - GABA

KW - type 1 cannabinoid receptor (CB)

KW - whole cell recordings

U2 - 10.1111/adb.12369

DO - 10.1111/adb.12369

M3 - Journal article

C2 - 26786379

AN - SCOPUS:85017287704

SN - 1355-6215

VL - 22

SP - 766

EP - 778

JO - Addiction Biology

JF - Addiction Biology

IS - 3