Hyperthermia induced by amphetamine, p-chloroamphetamine and fenfluramine in the rat-1.
Hyperthemia was elicited in rats by the subcutaneous injection of 4 mg/kg (+)-amphetamine, 4 mg/kg (+)-p-chloroamphetamine, or 8 mg/kg fenfluramine. This hyperthermia could be abolished by oral pretreatment with 300 mg/kg p-chlorophenylalanine. Cyproheptadine, at a dose of 0.05 mg/kg, completely inhibited the response induced by p-chloroamphetamine, but a dose of 0.4 mg/kg was necessary in the case of amphetamine and fenfluramine. Protection against hyperthermia by p-chloroamphetamine was also provided by chloroimipramine. Hypothalamic turnover of 5-HT was enhanced by all three amphetamines. alpha-Methyltyrosine and disulfiram had no effect on the hyperthemia induced by the amphetamines, FLA-63 seemed even to enhance it. Haloperidol, in the dose range of 0.1 -0.4 mg/kg, attenuated the hyperthermia induced by amphetamine and p-chloroamphetamine, but not that induced by fenfluramine. The results point to a central origin of the hyperthemia induced by amphetamine, p-chloroamphetamine and fenfluramine. In the mediation of this effect, 5-HT and, to a lesser degree, dopamine seem to play an important role.
D000661:Amphetamine / Q000037:antagonists & inhibitors*; D000662:Amphetamines; D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D002997:Clomipramine / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D003864:Depression, Chemical; D004221:Disulfiram / Q000494:pharmacology; D004298:Dopamine; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D005277:Fenfluramine / Q000037:antagonists & inhibitors*; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D008781:Methyltyrosines / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013268:Stimulation, Chemical; D013997:Time Factors; D010133:p-Chloroamphetamine
D000662:Amphetamines; D008781:Methyltyrosines; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D005277:Fenfluramine; D003533:Cyproheptadine; D012701:Serotonin; D010133:p-Chloroamphetamine; D000661:Amphetamine; D006220:Haloperidol; D002997:Clomipramine; D010134:Fenclonine; D004221:Disulfiram; D004298:Dopamine