5-HT1A and 5-HT2 receptors mediate hypo- and hyperthermic effects of tryptophan in pargyline-pretreated rats.
Mechanisms of tryptophan (a 5-HT precursor)-induced changes in body temperature were investigated in rats pretreated with pargyline, a monoamine oxidase inhibitor (MAO-I). Tryptophan (100 mg/kg, i.p.) did not affect the body temperature in rats, but it produced significant hypothermia followed by marked hyperthermia and higher mortality in the pargyline-pretreated rats. 5-HT depletion with p-chlorophenylalanine (p-CPA, 100 mg/kg/day for 3 days) significantly suppressed not only the body temperature change but also the mortality and 5-HT syndrome following tryptophan plus pargyline administration. Although propranolol (10 mg/kg, i.p.), a beta-adrenoceptor antagonist, did not alter the hypothermia caused by tryptophan in the pargyline-pretreated rats, pindolol (2 mg/kg, S.C.), a 5-HT1A receptor and beta-adrenoceptor antagonist, suppressed the hypothermia but not the hyperthermia or mortality caused by the same treatment. On the other hand, spiperone and ketanserin, 5-HT2 receptor antagonists, at doses of 3 mg/kg, potentiated the hypothermia and completely suppressed the hyperthermia and mortality caused by tryptophan in the pargyline-pretreated rats. These results suggest that tryptophan-induced hypo- and hyperthermia are mediated by 5-HT1A and 5-HT2 receptors, respectively, in the pargyline-pretreated pretreated rats.
Abdel-Fattah
A F
AF
Division of Pharmacology, Research Institute for Wakan Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Japan.
Matsumoto
K
K
el-Hady
K A
KA
Watanabe
H
H
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology*; D010869:Pindolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D014364:Tryptophan / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity
D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D013134:Spiperone; D014364:Tryptophan; D007650:Ketanserin; D010293:Pargyline; D011433:Propranolol; D010869:Pindolol; D010134:Fenclonine