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.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Cracow.
Moryl
E
E
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; C018406:1-(3-trifluoromethylphenyl)piperazine; D005277:Fenfluramine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; C015068:1-(3-chlorophenyl)piperazine