Effect of the combination of naltrexone and baclofen, on acquisition of alcohol drinking behavior in alcohol-preferring rats.
Recent surveys suggest that positive outcomes in the pharmacotherapy of alcoholism may be obtained through drug combinations. The present study evaluated the effect of the combination of the opioid receptor antagonist, naltrexone, with the GABA(B) receptor agonist, baclofen, on the acquisition of alcohol drinking behavior in Sardinian alcohol-preferring (sP) rats. Rats were treated with either saline, 0.5 mg/kg naltrexone, 1mg/kg baclofen, or 0.5 mg/kg naltrexone plus 1mg/kg baclofen once a day for 10 days. Alcohol was offered immediately after the first drug injection under the 2-bottle regimen. Alcohol intake in saline-treated rats rose to 5-6 g/kg/day within a few days, indicative of a rapid acquisition of alcohol drinking behavior. Neither naltrexone nor baclofen, when given alone, affected alcohol drinking behavior. In contrast, the drug combination resulted in a significant reduction in daily alcohol intake and retardation in the acquisition of alcohol drinking behavior. These results suggest that combination of naltrexone plus baclofen may result in a synergistic reduction in alcohol intake in sP rats. These results are discussed in terms of naltrexone and baclofen exerting a concomitant and reciprocally potentiating inhibitory action on alcohol-induced activation of mesolimbic dopamine transmission.
Colombo
Giancarlo
G
C.N.R. Institute of Neuroscience, Section of Cagliari, Viale Diaz 182, 1-09126 Cagliari, Italy. colomb@unica.it
Serra
Salvatore
S
Vacca
Giovanni
G
Carai
Mauro A M
MA
Gessa
Gian Luigi
GL
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics*; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage*; D051381:Rats
D009271:Naltrexone; D001418:Baclofen