Effects of 5-HT-1A receptor agonists on ethanol preference in the rat

Pharmacological manipulation of brain serotonin (5-HT) neurons has recently become recognized as an important approach in the treatment of ethanol (ET-OH) dependence. In the present study, we observed the effects of three agonists of 5-HT-1A receptor subtype, 8-OHDPAT, buspirone, and NDO-008, on ET-OH preference in Wistar male rats. Animals received ET-OH intragastrically during the first week of the experiment, and then during 2 consecutive weeks, the only source of fluid (23 h/d) was 5% and 8% wt/vol ET-OH solution, respectively. Then the animals were presented with a free-choice between water and 8% ET-OH solution for a 1-week period. Based on the baseline recordings, two groups of rats were formed: a high preference group (ET-OH intake greater than 50% of total daily fluid intake) and a low preference group of rats (ET-OH intake less than 20%). During week 5 of the experiment, animals were treated with 5-HT receptor agonists (subcutaneous injections twice daily for 4 days). The treatment caused a significant reduction of ET-OH intake in the high preference group, but caused no change in the remaining groups. The effect of highly selective 5-HT-1A receptor agonist, 8-OHDPAT, on ET-OH consumption in the high preference group was antagonized by cyanopindolol, a nonselective antagonist of 5-HT-1 receptor subtype. Our results support the hypothesis that activation of 5-HT-1A receptors reduces ET-OH preference.