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Involvement of the endogenous cannabinoid system in the effects of alcohol in the mesolimbic reward circuit: electrophysiological evidence in vivo

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Abstract

Rationale

Several lines of evidence indicate that the endogenous cannabinoid system is involved in the pharmacological and behavioural effects of alcohol. The mesolimbic dopaminergic (DA) system and the nucleus accumbens (NAc) process rewarding properties of drugs of abuse, including alcohol and cannabinoids, whereas endocannabinoids in these regions modulate synaptic function and mediate short- and long-term forms of synaptic plasticity.

Objectives

The present study was designed to investigate the contribution of the endogenous cannabinoid system in alcohol electrophysiological effects in the mesolimbic reward circuit.

Methods

We utilized extracellular single cell recordings from ventral tegmental area (VTA) DA and NAc neurons in anesthetized rats. DA neurons were antidromically identified as projecting to the shell of NAc, whereas NAc putative medium spiny neurons were identified by their evoked responses to basolateral amygdala (BLA) stimulation.

Results

Alcohol stimulated firing rate of VTA DA neurons and inhibited BLA-evoked NAc neuron spiking responses. The cannabinoid type-1 receptor (CB1) antagonist rimonabant (SR141716A) fully antagonized alcohol effect in both regions. In the NAc, either inhibition of the major catabolic enzyme of the endocannabinoid anandamide, the fatty-acid amyd hydrolase, with URB597 or a pretreatment with the CB1 receptor agonist WIN55212-2 significantly depressed alcohol-induced effects in the NAc.

Conclusions

These results corroborate the notion of the involvement of endocannabinoids and their receptors in the actions of alcohol and highlight the endocannabinoid system as a valuable target in the therapy for alcoholism.

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Acknowledgements

This work was supported by the grants of the Assessorato Igiene e Sanità (Regione Autonoma della Sardegna), PRIN 2003, FIRB 2001 (Italian Ministry of University). We wish to thank Sanofi-Aventis and, in particular, Dr. G. Le Fur for the generous gift of rimonabant and Mr. Stefano Aramo and Mrs. Barbara Tuveri for their skilled technical assistance.

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Authors and Affiliations

  1. B.B. Brodie Department of Neuroscience, University of Cagliari, Cittadella Universitaria di Monserrato, 09042, Monserrato, CA, Italy

    Simona Perra, Giuliano Pillolla, Miriam Melis, Gian Luigi Gessa & Marco Pistis

  2. Center of Excellence “Neurobiology of Addiction”, University of Cagliari, 09042, Monserrato, CA, Italy

    Simona Perra, Giuliano Pillolla, Miriam Melis, Anna Lisa Muntoni, Gian Luigi Gessa & Marco Pistis

  3. C.N.R. Institute of Neuroscience, section of Cagliari, University of Cagliari, 09042, Monserrato, CA, Italy

    Anna Lisa Muntoni & Gian Luigi Gessa

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  1. Simona Perra
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  2. Giuliano Pillolla
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  3. Miriam Melis
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  4. Anna Lisa Muntoni
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  5. Gian Luigi Gessa
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  6. Marco Pistis
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Correspondence to Marco Pistis.

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Perra, S., Pillolla, G., Melis, M. et al. Involvement of the endogenous cannabinoid system in the effects of alcohol in the mesolimbic reward circuit: electrophysiological evidence in vivo. Psychopharmacology 183, 368–377 (2005). https://doi.org/10.1007/s00213-005-0195-0

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