Effects of Ro 15-4513, fluoxetine and desipramine on the intake of ethanol, water and food by the alcohol-preferring (P) and -nonpreferring (NP) lines of rats

The effects of the IP administration of RO 15-4513 (1,2 and 4 mg/kg), fluoxetine (5 and 10 mg/kg) and desipramine (5 and 10 mg/kg) on the intake of 10% ethanol, H₂O and food were determined in the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats with daily access to fluids being limited to single 2-hour sessions. The imidazobenzodiazepine Ro 15-4513 (a partial inverse benzodiazepine agonist) significantly reduced the intake of 10% ethanol by the P rats to 50–60% of control levels in the first 30 minutes without altering food or H₂O intake. The attenuating actions of 2 mg/kg Ro 15-4513 on ethanol intake could be completely blocked by the central benzodiazepine receptor antagonist Ro 15-1788 (10 mg/kg). Ro 15-1788, by itself, produced no effects on alcohol and H₂O consumption. The 5 mg/kg dose of fluoxetine significantly reduced 10% ethanol intake by the P rats to 20% of control values without altering either H₂O or food consumption. The 10 mg/kg dose of fluoxetine further reduced ethanol intake by the P rats, but this dose also reduced daily food intake to approximately 70% of normal. Desipramine at both doses significantly (p<0.05) reduced both ethanol and food uptake by the P rats and had a tendency to reduce H₂O consumption as well. In general, the three drugs had effects in the NP rats similar to those observed for the P group, although the effects on 10% ethanol intake were difficult to compare because of the low, variable intake of alcohol by the NP group. The data are consistent with the involvement of serotonin and the GABA-benzodiazepine receptor complex in alcohol drinking behavior.