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.
Kostowski
W
W
Institute of Psychiatry and Neurology, Department of Pharmacology and Physiology of the Nervous System, Warsaw, Poland.
Dyr
W
W
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D004326:Drinking; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D002839:Chromans; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C071048:3-propylamino-5-hydroxychroman; D000431:Ethanol; C047975:cyanopindolol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol; D002065:Buspirone