Selective desensitization of serotonin (5-HT) receptor-mediated hyperthermia by mianserin and other 5-HT antagonists.
Hyperthermic responses to 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212) and hypothermic responses to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were assessed in rats as an in vivo index of the responsiveness of 5-HT2 and 5-HT1A receptors, respectively. Forty-eight hours after a single injection of mianserin, there was a shift to the right in the dose-response relationship for MK-212-induced hyperthermia. The hyperthermic response to MK-212 was attenuated 1 hr and 48 hr (but not 8, 24 or 96 hr) after the administration of mianserin. The hyperthermic effect of 5-methoxy-N,N-dimethyltryptamine (5MeODMT) also was diminished 48 hr after administration of mianserin. However, mianserin did not alter the hypothermic response to 8-OH-DPAT. A diminished hyperthermic effect of MK-212 also was observed 48 hr after a single injection of loxapine, methysergide, pizotifen and ketanserin. It is concluded that there is a selective decrease in the responsiveness of the 5-HT2 receptors mediating MK-212-induced hyperthermia, 48 hr after a single injection of mianserin or other selected 5-HT antagonists. Moreover, MK-212-induced hyperthermia appears to be a functional measure of the reported decrease in the number of 5-HT2 receptors, 48 hr after a single injection of mianserin.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced*; D008297:Male; D008803:Mianserin / Q000494:pharmacology*; D011719:Pyrazines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology
D011719:Pyrazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D008803:Mianserin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin