Spiroxatrine augments fluoxetine-induced reduction of ethanol intake by the P line of rats

The present study was undertaken to determine if spiroxatrine, a reported 5-HT1A antagonist, could block the attenuating effects of fluoxetine (a 5-HT uptake inhibitor) on voluntary ethanol intake by the selectively bred alcohol-preferring P line of rats. Fluoxetine (10 mg/kg, IP) significantly reduced the intake of 10% ethanol by P rats approximately 50% during the 4-hour period of alcohol availability. Spiroxatrine (4 mg/kg, IP) was without effect on ethanol intake when given alone. However, when given 5 minutes before fluoxetine (10 mg/kg, IP), this dose of spiroxatrine augmented the reduction of ethanol intake to approximately 15% of control values after 4 hours. Similar experiments conducted with 1 mg/kg (IP) 8-hydroxy-2(di-N-propylamino) tetralin (DPAT) demonstrated that this 5-HT1A agonist also enhanced the attenuating effects of fluoxetine on ethanol intake. Likewise, spiroxatrine augmented the DPAT reduction of alcohol intake. Spiroxatrine enhanced the effect of DPAT and fluoxetine on food intake as it did on ethanol intake. The results suggest that spiroxatrine behaved as a partial agonist and/or modulator and not as an antagonist at 5-HT1A receptors under the present experimental conditions.