Suppression of the hypo- and hyperthermic responses to 5-HT agonists following the repeated administration of monoamine oxidase inhibitors

Hypo- and hyperthermic responses resulting from the activation of putative 5-HT_1A and 5-HT₂ receptors, respectively, were examined after the chronic treatment of rats with monoamine oxidase inhibitors. The treatment of rats for 4 or 7 days with nialamide (40 mg/kg, twice daily) resulted in a suppression of the hypothermic effect of the 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.05-0.25 mg/kg, SC). The decrease in body temperature elicited by a low dose of 5-methoxy-N, N-dimethyltryptamine (5MeODMT, 1 mg/kg) also was diminished in rats treated chronically with nialamide. The administration of a high dose of 5MeODMT (5 mg/kg) resulted in a hyperthermic response, which was also attenuated after the repeated administration of nialamide. The repeated administration of clorgyline (a selective inhibitor of type A MAO) or deprenyl (a selective inhibitor of type B MAO) failed to alter the hypothermic effect of 8-OH-DPAT. However, in animals treated chronically with both clorgyline and deprenyl, a suppressed response to 8-OH-DPAT was observed. In view of the concept that the hypo- and hyperthermic responses to 5-HT agonists are mediated by 5-HT_1A and 5-HT₂ receptor subtypes, respectively, it is concluded that the responsiveness of these 5-HT receptor subtypes involved in thermoregulatory responses is decreased following chronic treatment of rats with monoamine oxidase inhibitors. It appears that inhibition of both type A and B MAO is necessary for this desensitization process.