ly-53857 and Fever

The effects of a serotonin (5-hydroxytryptamine, 5-HT)-releasing drug, p-chloroamphetamine (PCA), on body temperature were investigated in mice. PCA induced hyperthermia in mice. PCA-induced hyperthermia was inhibited by the 5-HT(2A/2B/2C) receptor antagonist, 4-isopropyl-7-methyl-9-(2-hydroxy-1-methyl-propoxycarbonyl)-4,6A,7 , 8,9,10,10A-octahydro-indolo[4,3-FG]quinolone maleate (LY53857). The 5-HT(2A) receptor antagonist, ketanserin, reduced the PCA-induced hyperthermia, while the 5-HT(2B/2C) receptor antagonist, N-3-pyridinyl-3,5-dihydro-5-methyl-benzo[1,2-b:4, 5-b']dipyrrole-1(2H)-carboxamide (SB 206553), enhanced it. LY 53857, ketanserin and SB 206553 did not affect hyperactivity in mice treated with PCA. These results suggest that PCA-induced hyperthermia in mice is mediated by 5-HT(2A) receptors and is not related to changes in locomotor activity.

Topics: Animals; Body Temperature Regulation; Dose-Response Relationship, Drug; Ergolines; Fever; Indoles; Ketanserin; Male; Mice; Motor Activity; p-Chloroamphetamine; Pyridines; Receptors, Serotonin; Serotonin Agents; Serotonin Antagonists

8-OH-DPAT (2.5-10 mg/kg) and buspirone (10 mg/kg) but not 5,7-DHT (200 micrograms/mouse), pCPA (75 and 150 mg/kg, three times), ritanserin (0.1 and 0.2 mg/kg), LY 53857 (1.5 and 3 mg/kg), GR 38032 F (0.1-100 micrograms/kg), TFMPP (5 and 20 mg/kg) and mCPP (2.5 and 5 mg/kg) antagonized the rise in body temperature that occurs to the last mice removed from their group housing, which was termed as stress-induced hyperthermia (SIH). Ro 15-1788, at a dose which blocked the effect of diazepam on SIH, did not reverse the anxiolytic effect of buspirione. Instead, when cerebral 5-HT content was reduced to 50% by 5,7-DHT-induced lesion, the effect of buspirone on SIH was decreased. TFMPP 5 mg/kg did not shorten significantly the onset of SIH as could have been expected by an anxiogenic drug, while the dose of 20 mg/kg did not modify the pattern of SIH at all. The lower dose of TFMPP evoked a hyperthermic and the higher a hypothermic response.

Topics: 5,7-Dihydroxytryptamine; 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Anti-Anxiety Agents; Body Temperature Regulation; Buspirone; Diazepam; Ergolines; Fenclonine; Fever; Flumazenil; Imidazoles; Male; Mice; Ondansetron; Piperazines; Piperidines; Ritanserin; Serotonin; Serotonin Antagonists; Stress, Psychological; Tetrahydronaphthalenes