Antagonism of serotonin receptor mediated neuroendocrine and temperature responses by atypical neuroleptics in the rat

The ability of atypical and typical antipsychotics to antagonize serotonin (5-HT) receptor-mediated temperature and neuroendocrine responses was tested in rats. Clozapine, melperone and setoperone, three atypical neuroleptics, blocked in a dose-dependent manner, the hyperthermic response to the 5-HT agonist, MK-212, whereas chlorpromazine and haloperidol were ineffective. The hypothermic response to the 5-HT 1A agonist, 8-OH-DPAT, was unaltered by any of the atypical neuroleptics tested. Similarly, MK-212-induced corticosterone secretion was blocked in a dose-related manner by clozapine, melperone and setoperone but was relatively unaffected by either haloperidol or chlorpromazine. The increase in corticosterone secretion observed following 8-OH-DPAT administration was not attenuated by pretreatment with the atypical or typical antipsychotics tested. These data indicate that atypical neuroleptics are effective 5-HT 2 but not 5-HT 1A antagonists in vivo. Conversely, the typical neuroleptics, haloperidol and chlorpromazine do not block the 5-HT receptors involved in activation of the hypothalamic-pituitary-adrenal axis or thermoregulation.