A cannabinoid mechanism in relapse to cocaine seeking.
Treatment of cocaine addiction is hampered by high rates of relapse even after prolonged drug abstinence. This relapse to compulsive cocaine use can be triggered by re-exposure to cocaine, by re-exposure to stimuli previously associated with cocaine or by exposure to stress. In laboratory rats, similar events reinstate cocaine seeking after prolonged withdrawal periods, thus providing a model to study neuronal mechanisms underlying the relapse to cocaine. The endocannabinoid system has been implicated in a number of neuropsychiatric conditions, including drug addiction. The active ingredient of marijuana, Delta9-tetrahydrocannabinol, activates the mesolimbic dopamine (DA) reward system and has rewarding effects in preclinical models of drug abuse. We report here that the synthetic cannabinoid agonist, HU210 (ref. 13), provokes relapse to cocaine seeking after prolonged withdrawal periods. Furthermore, the selective CB1 receptor antagonist, SR141716A (ref. 14), attenuates relapse induced by re-exposure to cocaine-associated cues or cocaine itself, but not relapse induced by exposure to stress. These data reveal an important role of the cannabinoid system in the neuronal processes underlying relapse to cocaine seeking, and provide a rationale for the use of cannabinoid receptor antagonists for the prevention of relapse to cocaine use.
De Vries
T J
TJ
Research Institute Neurosciences Vrije Universiteit, Department of Medical Pharmacology, VU Medical Center, Amsterdam, The Netherlands. tj.de_vries.pharm@med.vu.nl
Shaham
Y
Y
Homberg
J R
JR
Crombag
H
H
Schuurman
K
K
Dieben
J
J
Vanderschuren
L J
LJ
Schoffelmeer
A N
AN
D000818:Animals; D001522:Behavior, Animal; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003042:Cocaine / Q000378:metabolism* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D004195:Disease Models, Animal; D013759:Dronabinol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012008:Recurrence; D000077285:Rimonabant
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; D003042:Cocaine; C062018:HU 211; D000077285:Rimonabant