Caffeine-induced increases in the brain and plasma concentrations of neuroactive steroids in the rat.
The effects of caffeine, a naturally occurring stimulant, on the brain and plasma concentrations of neuroactive steroids were examined in the rat. A single intraperitoneal injection of caffeine induced dose- and time-dependent increases in the concentrations of pregnenolone, progesterone, and 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) in the cerebral cortex. The increases were significant at a caffeine dose of 25 mg/kg and greatest (+188, +388, and +71%, respectively) at a dose of 100 mg/kg in rats killed 30 min after caffeine administration. Caffeine also increased the plasma concentrations of pregnenolone and progesterone with a dose-response relation similar to that observed in the brain, whereas the caffeine-induced increase in the plasma concentration of allopregnanolone was maximal at a dose of 50 mg/kg. Caffeine increased the plasma concentration of corticosterone, but it had no effect on the brain or plasma concentrations of 3alpha, 21-dihydroxy-5alpha-pregnan-20-one and dehydroepiandrosterone. Moreover, the brain and plasma concentrations of pregnenolone, progesterone, and allopregnanolone were not affected by caffeine in adrenalectomized-orchiectomized rats. These results suggest that neuroactive steroids may modulate the stimulant and anxiogenic effects of caffeine.
Concas
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Department of Psychiatry, University of California, San Diego, CA 92161, USA. aconcas@unica.it
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Sogliano
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Serra
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Purdy
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Biggio
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011280:Pregnanolone / Q000378:metabolism*; D011284:Pregnenolone / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002110:Caffeine; D011374:Progesterone; D011284:Pregnenolone; D011280:Pregnanolone