Baclofen reduces ethanol intake in high-alcohol-drinking University of Chile bibulous rats.
ABSTRACT Treatment with gamma-aminobutiric acid (GABA(B)) receptor agonist, +/-baclofen, has been shown to reduce ethanol intake in selectively bred Sardinian alcohol-preferring rats. The general goal of the present study was to characterize the high ethanol consumption high-alcohol-drinking University of Chile bibulous (UChB) rats with regard to the anti-alcohol effect of GABA(B) receptor stimulation. UChB rats were treated with the more active enantiomer of baclofen [R(+)-baclofen; at a dose of 1.0, 2.0 or 3.0 mg/kg] administered intraperitoneally once daily for four consecutive days or a single dose. When comparing ethanol and saccharin consumption in a free-choice regimen with unlimited access 24 hours/day, the dose of baclofen required to attenuate ethanol consumption significantly was 1.0 mg/kg administered once a day for three consecutive days while the dose that was sufficient to affect saccharin consumption significantly was 2.0 mg/kg, indicating that baclofen was more potent in reducing ethanol intake by UChB rats than reducing saccharin consumption. The reduction of ethanol or saccharin intake can not be attributed to baclofen-induced motor impairment, since baclofen (1.0, 2.0 or 3.0 mg/kg) did not alter spontaneous locomotor activity in UChB rats. Baclofen dose-dependently suppressed the motor activity stimulated by ethanol administration, a phenomenon mediated by activation of the mesolimbic dopamine system. In conclusion, these results showed that the activation of GABA(B) receptor by R(+)-baclofen reduced ethanol and saccharin consumption, as well as ethanol-induced motor stimulation, implicating the GABA(B) receptor in the neural substrates mediating effects that sustain voluntary ethanol in take in UChB rats.
Quintanilla
María E
ME
Program of Molecular and Clinical Pharmacology, Faculty of Medicine, University of Chile, Santiago, Chile. equintanilla@med.uchile.cl
Perez
Elizabeth
E
Tampier
Lutske
L
D000437:Alcoholism / Q000517:prevention & control*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology* / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D002755:Choice Behavior; D004195:Disease Models, Animal; D000431:Ethanol; D008124:Locomotion / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D012439:Saccharin / Q000008:administration & dosage
D009125:Muscle Relaxants, Central; D011963:Receptors, GABA-A; D000431:Ethanol; D012439:Saccharin; D001418:Baclofen