Boosting effect of morphine on alcohol drinking is suppressed not only by naloxone but also by the cannabinoid CB1 receptor antagonist, SR 141716.
The present study investigated the effect of the cannabinoid CB(1) receptor antagonist, SR 141716 (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide), on the ability of low and high doses of morphine to, respectively, augment and suppress voluntary alcohol intake in selectively bred Sardinian alcohol-preferring rats. Acute administration of a low dose of morphine (1 mg/kg, s.c.) produced a specific and marked increase in alcohol intake, which correlated with an increase in blood alcohol levels and was prevented by either SR 141716 (0.3 mg/kg, i.p.) or naloxone (0.1 mg/kg, i.p.). A higher dose (10 mg/kg, s.c.) of morphine reduced both alcohol and food intakes and produced sedation and hypomotility. The suppressant effect of morphine on alcohol intake was blocked by naloxone (0.1 mg/kg, i.p.) but not by SR 141716 (0.3 mg/kg, i.p.). These results are in agreement with those showing the ability of SR 141716 to antagonize the appetitive and positive reinforcing properties of morphine and add further support to the hypothesis of the existence of a functional link between the action of opioids and of cannabinoids.
Vacca
Giovanni
G
Neuroscienze S.c.a r.l., Via Palabanda 9, I-09123, Cagliari, Italy.
Serra
Salvatore
S
Brunetti
Giuliana
G
Carai
Mauro A M
MA
Gessa
Gian Luigi
GL
Colombo
Giancarlo
G
D000428:Alcohol Drinking / Q000097:blood* / Q000235:genetics; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000502:physiology; D000077285:Rimonabant
D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D009270:Naloxone; D009020:Morphine; D000077285:Rimonabant