Effects of fluoxetine given chronically on the responsiveness of 5-HT receptor subpopulations to their agonists.

The effect of chronic treatment (5 and 10 mg/kg i.p., twice daily, 14 days) with fluoxetine (FLU), an antidepressant drug which selectively inhibits the reuptake of 5-hydroxytryptamine (5-HT), on the responsiveness of 5-HT receptor subpopulations to their agonists in rats and mice was examined. FLU had no effect on the hypothermia (in mice) and the behavioural syndrome (in rats) induced by 8-OH-DPAT (a 5-HT1A agonist). The m-CPP-induced hypothermia in mice (a 5-HT1B effect) was increased by FLU given chronically. FLU in a single dose decreased that effect. FLU given chronically attenuated the m-CPP-induced hypoactivity in rats (a 5-HT1C effect). The effects mediated by 5-HT2 receptors (L-5-HTP-induced head twitches in mice; fenfluramine-, m-CPP- and TFMPP-induced hyperthermias in rats) were reduced by chronic FLU. The above results indicate that FLU given chronically has no effect on the responsiveness of 5-HT1A receptors, increases the responsiveness of 5-HT1B receptors and decreases those of 5-HT1C and 5-HT2 receptors.