Functional interaction between opioid and cannabinoid receptors in drug self-administration.
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.
Navarro
M
M
Departamentos de Psicobiologia and Fisiologia, Universidad Complutense de Madrid, 28223 Madrid, Spain.
Carrera
M R
MR
Fratta
W
W
Valverde
O
O
Cossu
G
G
Fattore
L
L
Chowen
J A
JA
Gomez
R
R
del Arco
I
I
Villanua
M A
MA
Maldonado
R
R
Koob
G F
GF
Rodriguez de Fonseca
F
F
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002186:Cannabinoids / Q000037:antagonists & inhibitors; D002421:Caudate Nucleus / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D003932:Heroin / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D006556:Heroin Dependence / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011699:Putamen / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D000077285:Rimonabant; D012646:Self Administration; D020665:Septum of Brain / Q000378:metabolism
D002186:Cannabinoids; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D011957:Receptors, Opioid; D009270:Naloxone; D003932:Heroin; D009020:Morphine; D000077285:Rimonabant