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The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9 tetrahydrocannabinol (THC) in squirrel monkeys.
Psychopharmacology (Berl). 2004 Apr; 173(1-2):186-94.P

Abstract

RATIONALE

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 Delta(9)-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.

OBJECTIVES

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

METHODS

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 microg/kg per injection) were studied.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

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, Baltimore, MD 21224, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14668977

Citation

Justinova, Zuzana, et al. "The Opioid Antagonist Naltrexone Reduces the Reinforcing Effects of Delta 9 Tetrahydrocannabinol (THC) in Squirrel Monkeys." Psychopharmacology, vol. 173, no. 1-2, 2004, pp. 186-94.
Justinova Z, Tanda G, Munzar P, et al. The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9 tetrahydrocannabinol (THC) in squirrel monkeys. Psychopharmacology (Berl). 2004;173(1-2):186-94.
Justinova, Z., Tanda, G., Munzar, P., & Goldberg, S. R. (2004). The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9 tetrahydrocannabinol (THC) in squirrel monkeys. Psychopharmacology, 173(1-2), 186-94.
Justinova Z, et al. The Opioid Antagonist Naltrexone Reduces the Reinforcing Effects of Delta 9 Tetrahydrocannabinol (THC) in Squirrel Monkeys. Psychopharmacology (Berl). 2004;173(1-2):186-94. PubMed PMID: 14668977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9 tetrahydrocannabinol (THC) in squirrel monkeys. AU - Justinova,Zuzana, AU - Tanda,Gianluigi, AU - Munzar,Patrik, AU - Goldberg,Steven R, Y1 - 2003/12/11/ PY - 2003/07/23/received PY - 2003/10/24/accepted PY - 2003/12/12/pubmed PY - 2004/8/7/medline PY - 2003/12/12/entrez SP - 186 EP - 94 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 173 IS - 1-2 N2 - RATIONALE: 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 Delta(9)-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. OBJECTIVES: To study the effects of naltrexone, an opioid antagonist, on THC self-administration behavior in squirrel monkeys. METHODS: 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 microg/kg per injection) were studied. RESULTS: 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. CONCLUSIONS: 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/14668977/The_opioid_antagonist_naltrexone_reduces_the_reinforcing_effects_of_Delta_9_tetrahydrocannabinol__THC__in_squirrel_monkeys_ L2 - https://dx.doi.org/10.1007/s00213-003-1693-6 DB - PRIME DP - Unbound Medicine ER -