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The Journal of Neuroscience, July 15, 2001, 21(14):5344-5350

Functional Interaction between Opioid and Cannabinoid Receptors in Drug Self-Administration

M. Navarro¹, M. R. A. Carrera³, W. Fratta⁴, O. Valverde⁵, G. Cossu⁴, L. Fattore⁴, J. A. Chowen⁶, R. Gómez¹, I. del Arco^{1, 7}, M. A. Villanúa², R. Maldonado⁵, G. F. Koob³, and F. Rodríguez de Fonseca^{1, 7}

Departamentos de ¹ Psicobiología and ² Fisiología, Universidad Complutense de Madrid, 28223 Madrid, Spain, ³ Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, ⁴ Department of Neuroscience, University of Cagliary, Sardinia, 09124 Italy, ⁵ Departamento de Farmacología, Universidad Pompeu Fabra de Barcelona, 08003 Spain, ⁶ Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, 28002 Spain, and ⁷ Fundación Hospital Carlos Haya, 29010 Málaga, Spain

The present study was designed to explore the relationship between the cannabinoid and opioid receptors in animal models of opioid-induced reinforcement. The acute administration of SR141716A, a selective central cannabinoid CB1 receptor antagonist, blocked heroin self-administration in rats, as well as morphine-induced place preference and morphine self-administration in mice. Morphine-dependent animals injected with SR141716A exhibited a partial opiate-like withdrawal syndrome that had limited consequences on operant responses for food and induced place aversion. These effects were associated with morphine-induced changes in the expression of CB1 receptor mRNA in specific nuclei of the reward circuit, including dorsal caudate putamen, nucleus accumbens, and septum. Additionally, the opioid antagonist naloxone precipitated a mild cannabinoid-like withdrawal syndrome in cannabinoid-dependent rats and blocked cannabinoid self-administration in mice. Neither SR141716A nor naloxone produced any intrinsic effect on these behavioral models. The present results show the existence of a cross-interaction between opioid and cannabinoid systems in behavioral responses related to addiction and open new strategies for the treatment of opiate dependence.

Key words: addiction; cannabinoid; drug abuse; opioid; rat; mice; self-administration

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21145344-07$05.00/0

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