Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system

Simona Perra, Giuliano Pillolla, Antonio Luchicchi, Marco Pistis

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol.

METHODS: We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens.

RESULTS: Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 +/- 16% of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 +/- 18% of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose-response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 +/- 16% of baseline firing at 0.5 g/kg, p < 0.05).

CONCLUSIONS: Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism.

Original languageEnglish
Pages (from-to)443-9
Number of pages7
JournalAlcoholism, Clinical and Experimental Research
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

Cite this

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title = "Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system",
abstract = "BACKGROUND: A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol.METHODS: We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens.RESULTS: Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 +/- 16{\%} of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 +/- 18{\%} of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose-response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 +/- 16{\%} of baseline firing at 0.5 g/kg, p < 0.05).CONCLUSIONS: Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism.",
keywords = "Action Potentials, Alcohol Drinking, Amygdala, Animals, Cannabinoid Receptor Modulators, Dose-Response Relationship, Drug, Endocannabinoids, Ethanol, Male, Neural Inhibition, Neural Pathways, Neurons, Nucleus Accumbens, Piperidines, Pyrazoles, Rats, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't",
author = "Simona Perra and Giuliano Pillolla and Antonio Luchicchi and Marco Pistis",
year = "2008",
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language = "English",
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pages = "443--9",
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Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat : involvement of the endocannabinoid system. / Perra, Simona; Pillolla, Giuliano; Luchicchi, Antonio; Pistis, Marco.

In: Alcoholism, Clinical and Experimental Research, Vol. 32, No. 3, 03.2008, p. 443-9.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat

T2 - involvement of the endocannabinoid system

AU - Perra, Simona

AU - Pillolla, Giuliano

AU - Luchicchi, Antonio

AU - Pistis, Marco

PY - 2008/3

Y1 - 2008/3

N2 - BACKGROUND: A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol.METHODS: We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens.RESULTS: Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 +/- 16% of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 +/- 18% of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose-response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 +/- 16% of baseline firing at 0.5 g/kg, p < 0.05).CONCLUSIONS: Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism.

AB - BACKGROUND: A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol.METHODS: We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens.RESULTS: Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 +/- 16% of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 +/- 18% of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose-response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 +/- 16% of baseline firing at 0.5 g/kg, p < 0.05).CONCLUSIONS: Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism.

KW - Action Potentials

KW - Alcohol Drinking

KW - Amygdala

KW - Animals

KW - Cannabinoid Receptor Modulators

KW - Dose-Response Relationship, Drug

KW - Endocannabinoids

KW - Ethanol

KW - Male

KW - Neural Inhibition

KW - Neural Pathways

KW - Neurons

KW - Nucleus Accumbens

KW - Piperidines

KW - Pyrazoles

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptor, Cannabinoid, CB1

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/j.1530-0277.2007.00588.x

DO - 10.1111/j.1530-0277.2007.00588.x

M3 - Article

VL - 32

SP - 443

EP - 449

JO - Alcoholism, Clinical and Experimental Research

JF - Alcoholism, Clinical and Experimental Research

SN - 0145-6008

IS - 3

ER -