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Effect of the cannabinoid CB1 receptor antagonist SR-141716A on ethanol self-administration and ethanol-seeking behaviour in rats

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Abstract

Rationale

It has been suggested that endocannabinoid mechanisms are involved in the control of ethanol consumption.

Objectives

The aims of the present study were (1) to evaluate the role of the endocannabinoid system in the control of operant ethanol self-administration and in the reinstatement of ethanol seeking, when induced by stress or conditioned stimuli and (2) to offer new insights on the specificity of such a role.

Methods

Rats were administered intraperitoneally with the selective cannabinoid CB1 receptor antagonist, SR-141716A, 30 min before operant self-administration or reinstatement sessions. Two schedules of reinforcement, the fixed-ratio 1 (FR1) and the progressive ratio (PR), were used to study 10% (w/v) alcohol and 5.0% sucrose self-administration. NaCl (2% w/v) intake in sodium-depleted rats was studied only under the FR1 program.

Results

Treatment with SR-141716A (0.3–3.0 mg/kg) significantly attenuated FR1 alcohol self-administration and lowered the break point for ethanol under PR. SR-141716A also markedly inhibited the reinstatement of alcohol seeking elicited by presentation of cues predictive of drug availability. Conversely, the cannabinoid antagonist did not prevent the reinstatement of alcohol seeking induced by foot-shock stress. Lever pressing for sucrose under FR1 and PR schedules was also significantly decreased by SR-141716A treatment, whereas the drug modestly and only at the highest dose decreased 2% NaCl self-administration.

Conclusions

Results emphasize that endocannabinoid mechanisms play a major role in the control of ethanol self-administration and in the reinstatement of conditioned ethanol seeking. However, these effects extend to the control of operant behaviours motivated by natural rewards (i.e. sucrose). On the other hand, SR-141716A only weakly reduces NaCl self-administration in sodium-depleted rats, in which salt intake is largely controlled by homeostatic mechanisms. Overall, these observations demonstrate that the inhibition of operant behaviour following blockade of CB1 receptors by SR-141716A is linked to a reduction of reward-related responding and is not related to drug-induced motor deficits.

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Acknowledgements

This work was supported by grant from MIUR, Rome, Italy (COFIN 2002 to MM, FIRB 2002 to VC) and by the EU 5th Framework Program, grant QLRT-2001-01048 (TargAlc Consortium).

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Authors and Affiliations

  1. Department of Experimental Medicine and Public Health, University of Camerino, Via Scalzino 3, 62032, Camerino, Italy

    Daina Economidou, Laura Mattioli, Carlo Cifani, Marina Perfumi, Maurizio Massi & Roberto Ciccocioppo

  2. Department of Pharmacology of Natural Substances and General Physiology, University of Rome “La Sapienza”, Via A. Moro 5, 00185, Rome, Italy

    Vincenzo Cuomo

  3. Department of Biomedical Sciences, University of Foggia, Via Luigi Pinto, 71100, Foggia, Italy

    Luigia Trabace

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  1. Daina Economidou
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  2. Laura Mattioli
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  3. Carlo Cifani
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  4. Marina Perfumi
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  5. Maurizio Massi
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  6. Vincenzo Cuomo
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  7. Luigia Trabace
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  8. Roberto Ciccocioppo
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Correspondence to Roberto Ciccocioppo.

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Economidou, D., Mattioli, L., Cifani, C. et al. Effect of the cannabinoid CB1 receptor antagonist SR-141716A on ethanol self-administration and ethanol-seeking behaviour in rats. Psychopharmacology 183, 394–403 (2006). https://doi.org/10.1007/s00213-005-0199-9

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  • DOI: https://doi.org/10.1007/s00213-005-0199-9

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