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.
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 -
