The opioid antagonist naltrexone reduces the reinforcing effects of Δ⁹-tetrahydrocannabinol (THC) in squirrel monkeys

Authors: Justinova, Zuzana¹; Tanda, Gianluigi²; Munzar, Patrik¹; Goldberg, Steven³

Source: Psychopharmacology, Volume 173, Numbers 1-2, April 2004 , pp. 186-194(9)

Publisher: Springer

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Abstract:

Experimental evidence from animal studies suggests reciprocal functional interactions between endogenous brain cannabinoid and opioid systems. There is recent evidence for a role of the opioid system in the modulation of the reinforcing effects of synthetic cannabinoid CB1 receptor agonists in rodents. Since Δ⁹–tetrahydrocannabinol (THC), the natural psychoactive ingredient in marijuana, is actively and persistently self-administered by squirrel monkeys, this provides an opportunity to directly study involvement of opioid systems in the reinforcing effects of THC in non-human primates.

To study the effects of naltrexone, an opioid antagonist, on THC self-administration behavior in squirrel monkeys.

Monkeys pressed a lever for intravenous injections of THC under a ten-response, fixed-ratio (FR) schedule with a 60-s time-out after each injection. Effects of pre-session treatment with naltrexone (0.03–0.3 mg/kg intramuscularly, 15 min before session) for 5 consecutive days on self-administration of different doses of THC (2–8 µg/kg per injection) were studied.

Self-administration responding for THC was significantly reduced by pretreatment with 0.1 mg/kg naltrexone for five consecutive daily sessions. Naltrexone pretreatment had no significant effect on cocaine self-administration responding under identical conditions.

Self-administration behavior under a fixed-ratio schedule of intravenous THC injection was markedly reduced by daily pre-session treatment with naltrexone, but remained above saline self-administration levels. These findings demonstrate for the first time the modulation of the reinforcing effects of THC by an opioid antagonist in a non-human primate model of marijuana abuse.

Keywords: Δ9-Tetrahydrocannabinol (THC); Cocaine; Naltrexone; Drug self-administration; Squirrel monkeys; Marijuana

Document Type: Research article

DOI: 10.1007/s00213-003-1693-6

Affiliations: 1: 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, Baltimore, 2: Psychobiology Section, Medications Discovery Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA, 3: 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, Baltimore,

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