Self-administration of Delta(9)-tetrahydrocannabinol (THC)
by drug naive squirrel monkeys
Justinova Z, Tanda G, Redhi GH, Goldberg SR.
Preclinical Pharmacology Section,
Behavioral Neuroscience Research Branch,
Intramural Research Program,
National Institute on Drug Abuse,
National Institutes of Health,
Department of Health and Human Services,
5500 Nathan Shock Drive,
MD 21224, Baltimore, USA.
Psychopharmacology (Berl). 2003 Jun 24
ABSTRACTRATIONALE. Interest in therapeutic activities of cannabinoids has been restrained by the fact that they are most often mediated through activation of cannabinoid CB(1) receptors, the same receptors that mediate the effects of Delta(9)-tetrahydrocannabinol (THC) and are responsible for the abuse liability of marijuana. Persistent intravenous self-administration of THC by animals was first demonstrated in squirrel monkeys and shown to be mediated by CB(1) receptors, but monkeys in the study had a history of cocaine self-administration, raising the possibility that persistent neurobiological adaptations might subsequently predispose animals to self-administer THC. OBJECTIVES. To demonstrate persistent intravenous self-administration of THC in drug-naive squirrel monkeys. METHODS. Monkeys with no history of exposure to other drugs learned to press a lever for intravenous injections (0.2 ml in 0.2 s) of THC under a 10-response, fixed-ratio schedule with a 60-s time-out after each injection. Acquisition of THC self-administration was rapid and the final schedule was reached in 11-34 sessions. Dose of THC was then varied from 1 to 16 micro g/kg per injection with vehicle extinction following each dose of THC. RESULTS. THC maintained significantly higher numbers of self-administered injections per session and higher rates of responding than vehicle at doses of 2, 4 and 8 micro g/kg per injection, with maximal rates of responding at 4 micro g/kg per injection. Response rates, injections per session and total THC intake per session were two- to three-fold greater in monkeys with no history of exposure to other drugs compared to previous findings in monkeys with a history of cocaine self-administration. CONCLUSIONS. THC can act as an effective reinforcer of drug-taking behavior in monkeys with no history of exposure to other drugs, suggesting that self-administration of THC by monkeys provides a reliable animal model of human marijuana abuse.THC
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