Effects of sertraline and citalopram given repeatedly on the responsiveness of 5-HT receptor subpopulations.
The effect of repeated treatment (5 and 10 mg/kg, po, twice daily, 14 days) with sertraline and citalopram (antidepressants which selectively inhibit the reuptake of 5-hydroxytryptamine (5-HT)) on the responsiveness of different 5-HT receptors to their agonists, was examined in rats and mice. Sertraline and citalopram (both at a dose 5 and 10 mg/kg) antagonized (the first one more potently) the hypothermia induced in mice by 8-OH-DPAT (a 5-HT1A agonist), but not the behavioural syndrome induced in rats by this substance. The m-chlorophenylpiperazine-induced hypothermia in mice (a 5-HT1B effect) was increased by sertraline and citalopram (only in a dose of 10 mg/kg). Both antidepressants, given repeatedly (as well acutely) attenuated exploratory hypoactivity induced in rats by m-chlorophenylpiperazine (a 5-HT1C effect). L-5-HTP-induced head twitches in mice (5-HT2 effect) were antagonized dose-dependently by both repeated sertraline and citalopram. Both antidepressants (citalopram only in higher dose) reduced the fenfluramine-induced hyperthermia in rats (5-HT2 effect). The results indicate that sertraline and citalopram given repeatedly decrease the responsiveness of 5-HT1A (presynaptic) and 5-HT2 receptors but increase the responsiveness of 5-HT1B receptors to respective agonists.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Moryl
E
E
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects*; D020280:Sertraline; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D015283:Citalopram; D005277:Fenfluramine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015057:1-Naphthylamine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D006916:5-Hydroxytryptophan; D020280:Sertraline