Synergistic neurochemical and behavioral effects of fluoxetine and 5-HT1A receptor antagonists

We studied the ability of WAY 100635 {N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide}, 0.5 mg/kg, i.v. and (-)-5-Me-8-OH-DPAT {(-)-5-methyl-8-hydroxy-2-(di-n-propylamino)tetralin}, 3 mg/kg, i.v. two selective 5-HT1A receptor antagonists, to potentiate: (1) the enhancement of extracellular 5-HT levels ([5-HText]) induced by a single administration of 5 mg/kg i.p. fluoxetine using in vivo microdialysis in the ventral hippocampus of conscious rats, (2) the decrease in food intake induced by this antidepressant drug in food-deprived rats. The effects of fluoxetine were significantly potentiated, by 30-40%, by WAY 100635 as well as by (-)-5-Me-8-OH-DPAT in the two sets of experiments. Thus, fluoxetine increased [5-HText] in serotonergic nerve terminal areas and consequently, induced hypophagia, both effects being limited by indirect activation of somatodendritic 5-HT1A autoreceptors. (C) 1998 Elsevier Science B.V. All rights reserved.