Blockade of THC-seeking behavior and relapse in monkeys by the cannabinoid CB(1)-receptor antagonist rimonabant.
Accumulating evidence suggests the endocannabinoid system modulates environmental cues' ability to induce seeking of drugs, including nicotine and alcohol. However, little attention has been directed toward extending these advances to the growing problem of cannabis use disorders. Therefore, we studied intravenous self-administration of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, using a second-order schedule of drug seeking. Squirrel monkeys' lever responses produced only a brief cue light until the end of the session, when the final response delivered THC along with the cue. When a reinstatement procedure was used to model relapse following a period of abstinence, THC-seeking behavior was robustly reinstated by the cue or by pre-session administration of THC, other cannabinoid agonists, or morphine, but not cocaine. The cannabinoid antagonist rimonabant blocked cue-induced drug seeking, THC-induced drug seeking, and the direct reinforcing effects of THC. Thus, rimonabant and related medications might be effective as treatments for cannabinoid dependence.
Justinova
Zuzana
Z
Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Department of Health and Human Services, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Munzar
Patrik
P
Panlilio
Leigh V
LV
Yasar
Sevil
S
Redhi
Godfrey H
GH
Tanda
Gianluigi
G
Goldberg
Steven R
SR
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D003463:Cues; D004195:Disease Models, Animal; D013759:Dronabinol / Q000037:antagonists & inhibitors*; D004334:Drug Administration Schedule; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009020:Morphine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012054:Reinforcement, Psychology; D000077285:Rimonabant; D012453:Saimiri; D055502:Secondary Prevention; D012646:Self Administration
D000701:Analgesics, Opioid; D063385:Cannabinoid Receptor Modulators; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D009020:Morphine; D013759:Dronabinol; D000077285:Rimonabant