Suppression by baclofen of the stimulation of alcohol intake induced by morphine and WIN 55,212-2 in alcohol-preferring rats.
Administration of morphine and cannabinoids stimulates alcohol intake in rats. The present study investigated whether the promoting effect of morphine and of the cannabinoid receptor agonist, WIN 55,212-2 [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone], on alcohol intake was prevented by the gamma-aminobutyric (GABA)(B) receptor agonist, baclofen. Sardinian alcohol-preferring (sP) rats were given alcohol (10%, v/v) and water under the standard homecage two-bottle-free choice regimen with unlimited access for 24 h/day. Baclofen (0, 0.5 and 1 mg/kg; i.p.) was administered acutely 30 min before lights off. Morphine (0 and 1 mg/kg, s.c.) or WIN 55,212-2 (0 and 2 mg/kg, i.p.) was administered acutely 10 min after baclofen. Alcohol intake was recorded 60 min after lights off. As predicted, both morphine and WIN 55,212-2 produced a specific and marked increase in alcohol intake. Pretreatment with baclofen, which failed to alter alcohol intake when given alone, dose-dependently suppressed morphine- and WIN 55,212-2-induced promotion of alcohol drinking. These results suggest the involvement of the GABA(B) receptor in the neural circuitry mediating the stimulating effect of morphine and cannabinoids on alcohol consumption in sP rats.
Colombo
Giancarlo
G
Department of Neuroscience, C.N.R. Institute of Neuroscience, c/o "Bernard B. Brodie" University of Cagliari, Viale Diaz 182, Cagliari I-09126, Italy. colomb@unica.it
Serra
Salvatore
S
Vacca
Giovanni
G
Gessa
Gian Luigi
GL
Carai
Mauro A M
MA
D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058786:GABA-B Receptor Agonists; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D018080:Receptors, GABA-B / Q000502:physiology
D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D018080:Receptors, GABA-B; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009020:Morphine; D001418:Baclofen