Functional interaction between opioid and cannabinoid receptors in drug self-administration.

Abstract

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.

• Authors: M Navarro, M R Carrera, W Fratta, O Valverde, G Cossu, L Fattore, J A Chowen, R Gomez, I del Arco, M A Villanua, R Maldonado, G F Koob, F Rodriguez de Fonseca
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 21 Issue 14 Pg. 5344-50 (Jul 15 2001) ISSN: 1529-2401 [Electronic] United States
• PMID: 11438610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cannabinoids
• Narcotic Antagonists
• Piperidines
• Pyrazoles
• RNA, Messenger
• Receptors, Cannabinoid
• Receptors, Drug
• Receptors, Opioid
• Naloxone
• Heroin
• Morphine
• Rimonabant

Topics

• Animals
• Avoidance Learning (drug effects)
• Cannabinoids (antagonists & inhibitors)
• Caudate Nucleus (metabolism)
• Conditioning, Operant (drug effects)
• Disease Models, Animal
• Heroin (administration & dosage, antagonists & inhibitors)
• Heroin Dependence (metabolism)
• Male
• Mice
• Morphine (administration & dosage, antagonists & inhibitors)
• Morphine Dependence (metabolism)
• Naloxone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Nucleus Accumbens (metabolism)
• Piperidines (pharmacology)
• Putamen (metabolism)
• Pyrazoles (pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Receptors, Cannabinoid
• Receptors, Drug (antagonists & inhibitors, genetics, metabolism)
• Receptors, Opioid (metabolism)
• Rimonabant
• Self Administration
• Septum of Brain (metabolism)