Clozapine decreases rat brain dehydroepiandrosterone and dehydroepiandrosterone sulfate levels.
We examined the influence of the atypical antipsychotic agent clozapine compared to haloperidol, on levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate ester (both gamma-aminobutyric acid(A) (GABA(A)) receptor allosteric antagonists) in the rat cortex. i.p. injections of clozapine (5 and 15 mg/kg), but not haloperidol (1 mg/kg), for 8 days decreased rat brain cortical dehydroepiandrosterone and dehydroepiandrosterone sulfate levels. These findings support the role of neurosteroids and possibly GABA(A) receptor modulation in the mechanism of action of clozapine.
Nechmad
Allon
A
Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Beilinson Campus, Petah Tiqva, Israel.
Maayan
Rachel
R
Ramadan
Edward
E
Morad
Oren
O
Poyurovsky
Michael
M
Weizman
Abraham
A
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000032:analysis / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000032:analysis / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology
D018492:Dopamine Antagonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D003024:Clozapine; D006220:Haloperidol