title: The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9 tetrahydrocannabinol (THC) in squirrel monkeys.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.affiliation: 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.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Justinova
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Tanda
authors.forename: Patrik
authors.initials: P
authors.lastname: Munzar
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012453:Saimiri; D012646:Self Administration
chemical_list: D018712:Analgesics, Non-Narcotic; D000779:Anesthetics, Local; D009292:Narcotic Antagonists; D009271:Naltrexone; D013759:Dronabinol; D003042:Cocaine