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Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system.
Alcohol Clin Exp Res. 2008 Mar; 32(3):443-9.AC

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.

Authors+Show Affiliations

B.B. Brodie Department of Neuroscience and Centre of Excellence for Neurobiology of Addiction, University of Cagliari, Monserrato (CA), Italy.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18215217

Citation

Perra, Simona, et al. "Alcohol Inhibits Spontaneous Activity of Basolateral Amygdala Projection Neurons in the Rat: Involvement of the Endocannabinoid System." Alcoholism, Clinical and Experimental Research, vol. 32, no. 3, 2008, pp. 443-9.
Perra S, Pillolla G, Luchicchi A, et al. Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system. Alcohol Clin Exp Res. 2008;32(3):443-9.
Perra, S., Pillolla, G., Luchicchi, A., & Pistis, M. (2008). Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system. Alcoholism, Clinical and Experimental Research, 32(3), 443-9. https://doi.org/10.1111/j.1530-0277.2007.00588.x
Perra S, et al. Alcohol Inhibits Spontaneous Activity of Basolateral Amygdala Projection Neurons in the Rat: Involvement of the Endocannabinoid System. Alcohol Clin Exp Res. 2008;32(3):443-9. PubMed PMID: 18215217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system. AU - Perra,Simona, AU - Pillolla,Giuliano, AU - Luchicchi,Antonio, AU - Pistis,Marco, Y1 - 2008/01/22/ PY - 2008/1/25/pubmed PY - 2008/4/17/medline PY - 2008/1/25/entrez SP - 443 EP - 9 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 32 IS - 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. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/18215217/Alcohol_inhibits_spontaneous_activity_of_basolateral_amygdala_projection_neurons_in_the_rat:_involvement_of_the_endocannabinoid_system_ L2 - https://doi.org/10.1111/j.1530-0277.2007.00588.x DB - PRIME DP - Unbound Medicine ER -