Journal
NEUROPSYCHOPHARMACOLOGY
Volume 33, Issue 12, Pages 2870-2877Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2008.21
Keywords
cannabinoids; drug seeking; reinstatement; rimonabant; second-order schedule; self-administration
Categories
Funding
- Intramural Research Program of the National Institute on Drug Abuse
- NIH
- DHHS
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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.
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