Effects of some centrally active drugs on the allopregnanolone synthesis in rat brain.
Effects of antidepressants (desipramine, amitriptyline), anticonvulsants (phenytoin, diazepam, carbamazepine) and addictive drugs (amphetamine, morphine), used at a concentration of 100 microM on the conversion of [14C]-progesterone to 5alpha-pregnane-3,20-dione and allopregnanolone in slices of the frontal cortex and olfactory bulb from rat brain were studied. The synthesis of 5alpha-pregnane-3,20-dione and allopregnanolone was stronger in the olfactory bulb than in the frontal cortex. The biosynthesis of allopregnanolone in the frontal cortex was higher by 74, 109 and 187% when stimulated by amitriptyline, desipramine and carbamazepine, respectively, and, to a lesser degree, by phenytoin and morphine. Desipramine and morphine decreased the concentration of 5alpha-pregnane-3,20-dione. In the olfactory bulb, only carbamazepine enhanced allopregnanolone production, but none of the tested drugs had any effect on 5alpha-pregnane-3,20-dione synthesis. It is concluded that some psychotropic drugs may increase allopregnanolone synthesis by stimulating the activity of the enzyme, 3alpha-hydroxysteroid dehydrogenase, in the frontal cortex, and that this neurosteroid may be partly involved in the mechanism of action of the drugs under study.
Jaworska-Feil
L
L
Department of Endocrinology, Polish Academy of Sciences, Kraków.
Budziszewska
B
B
Leśkiewicz
M
M
Lasoń
W
W
D043582:5-alpha-Dihydroprogesterone; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011277:Pregnanediones / Q000378:metabolism; D011280:Pregnanolone / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D000928:Antidepressive Agents; D002491:Central Nervous System Agents; D000697:Central Nervous System Stimulants; D009294:Narcotics; D011277:Pregnanediones; D043582:5-alpha-Dihydroprogesterone; D011280:Pregnanolone