Effects of CB1 receptor antagonist within the nucleus accumbens on the acquisition and expression of morphine-induced conditioned place preference in morphine-sensitized rats.
It has been shown that cannabinoids interact with the opiate system in reward-related behaviors and in animal models of addiction. In the present study, the effects of bilateral intra-accumbal administration of AM251, a CB1 receptor antagonist, on the acquisition and expression of ineffective dose of morphine-induced conditioned place preference (CPP) in morphine-sensitized rats were investigated. 158 adult male albino Wistar rats were used in these experiments. Subcutaneous (s.c.) administration of morphine (0.25, 0.5, 0.75, 1, 2.5 and 5mg/kg) induced CPP only at the dose of 5mg/kg. In addition, repeated administration of morphine (5mg/kg; s.c.), once daily for 3 days followed by 5 days free of the opioid (sensitization period), increased conditioning response induced by ineffective doses of morphine (0.25, 0.5 and 0.75 mg/kg). Bilateral intra-accumbal administration of AM251 (5, 25 and 125 ng/0.5 microl per side) dose-dependently reduced the acquisition and expression of morphine-induced CPP in morphine-sensitized rats, while bilateral intra-accumbal administration of neither saline nor DMSO (0.5 microl/side) had effects on the acquisition and expression of morphine-induced CPP in sensitized rats. The results indicated that CB1 receptors within the nucleus accumbens are involved in the acquisition and expression of morphine-induced CPP in sensitized rats. Our findings also suggest the existence of cross-talk between cannabinoids and opiates on the sensitization to morphine and the implication of endocannabinoid system in the process of sensitization to opiates.
Azizi
Pegah
P
Neuroscience Research Center, Shahid Beheshti University, M.C., P.O. Box 19615-1178, Tehran, Iran.
Haghparast
Abbas
A
Hassanpour-Ezatti
Majid
M
D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D063385:Cannabinoid Receptor Modulators / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D018709:Statistics, Nonparametric
D063385:Cannabinoid Receptor Modulators; D009294:Narcotics; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D009020:Morphine