EFFECTS OF FLUOXETINE AND DESIPRAMINE ON PALATABILITY-INDUCED ETHANOL-CONSUMPTION IN THE ALCOHOL-NONPREFERRING (NP) LINE OF RATS

Three groups of NP rats (n = 5/group) received food, water and one of 3 Polycose solutions ad lib. One group received a solution containing 3% (w/v) Polycose, 0.125% (w/v) saccharin, 0.5% (w/v) NaCl (3% POL solution) to which ethanol was gradually added over three weeks until the concentration of 10% (v/v) ethanol (E) was reached (3% POL + E group). Alcohol ingestion by the 3% POL + E group reached an average of 9 g of ethanol/kg b.wt./day; the rats attained average blood alcohol concentrations of 61 ± 8 mg%. One control group (3% POL) was given the same solution as above but without ethanol. The second control group (17% POL) had access to a 17.6% Polycose solution supplemented with 0.125% saccharin and 0.5% NaCl and was isocaloric to the 3% POL + E solution. Although the three groups differed significantly in the amounts of food and Polycose solutions consumed, their total caloric intakes were equivalent. The IP administration of the serotonin (5-HT) uptake inhibitor fluoxetine (5 and 10 mg/kg) significantly reduced drinking of the group receiving the 3% POL + E solution by 23% and 67%, respectively, but did not alter intakes of the Polycose solutions by the 3% or 17% POL control groups. The IP administration of the norepinephrine (NE) uptake inhibitor desipramine (5 and 10 mg/kg) significantly reduced intake of the Polycose solution by the 17% POL group by 52 and 83%, respectively, but only the 10 mg/kg dose attenuated drinking of the solutions by the 3% POL and 3% POL + E groups. Both fluoxetine and desipramine decreased food intake of the 3% POL and 3% POL + E groups, while only desipramine suppressed food intake of the 17% POL rats. The data show that (a) NP rats can be induced to drink pharmacologically relevant amounts of ethanol when offered in a palatable solution, (b) fluoxetine preferentially reduces ethanol intake by NP rats through its actions on 5-HT systems that presumably mediate the aversive properties of ethanol, and (c) a carbohydrate-rich diet appears to alter the anorectic actions of NE and 5-HT uptake inhibitors in the NP rat. © 1990.