Facilitatory and inhibitory effects of harmaline on the tryptophan-induced 5-hydroxytryptamine syndrome and body temperature changes in pargyline-pretreated rats.

The effects of harmaline on tryptophan-induced 5-hydroxytryptamine (5HT) syndrome and body temperature changes in pargyline-pretreated rats were investigated. When administered i.p. 60 min after pargyline treatment (50 mg/kg, i.p.), tryptophan, at 100 mg/kg but not 10 mg/kg, induced the 5-HT syndrome. Tryptophan at 100 mg/kg also produced hypothermia followed by hyperthermia in pargyline-pretreated rats. Administration of harmaline (10 mg/kg, i.p.) 30 min after pargyline not only potentiated the 100 mg/kg tryptophan-induced 5-HT syndrome and body temperature changes, but also produced the syndrome following administration of 10 mg/kg tryptophan in pargyline-pretreated rats. In contrast, when administered 30 min before parygline, 10 mg/kg harmaline completely suppressed the syndrome and body temperature changes caused by mg/kg tryptophan. Tryptophan (100 mg/kg, i.p.) administration significantly increased 5-HT levels and decreased 5-hydroxyindole acetic and levels and 5-HT turnover in the brain of pargyline-pretreated rats. Harmaline administration 30 min after pargyline did not significantly affect the tryptophan-induced changes in 5-HT levels and 5-HT turnover, whereas when administered 30 min before pargyline, harmaline significantly blocked the effect of tryptophan. These results suggest that mechanisms underlying the inhibitory action of harmaline on the tryptophan-induced 5-HT syndrome and body temperature changes in pargyline-pretreated rats differ from those by which harmaline potentiates the effects of tryptophan.

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.