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-HT1A 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-HT2 but not 5-HT1A 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.
Nash
J F
JF
Case Western Reserve University, School of Medicine, Department of Psychiatry and Pharmacology, Cleveland, Ohio 44106.
Meltzer
H Y
HY
Gudelsky
G A
GA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D002090:Butyrophenones / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009490:Neurosecretory Systems / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014150:Antipsychotic Agents; D002090:Butyrophenones; D011719:Pyrazines; D011744:Pyrimidinones; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C045359:setoperone; D003024:Clozapine; D006220:Haloperidol; C008522:metylperon; D002746:Chlorpromazine; D003345:Corticosterone