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 s ingle intraperitoneal injection of caffeine induced dose- and time-dependen t increases in the concentrations of pregnenolone, progesterone, and 3 alph a-hydroxy-5 alpha-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 c oncentrations of pregnenolone and progesterone with a dose-response relatio n similar to that observed in the brain, whereas the caffeine-induced incre ase in the plasma concentration of allopregnanolone was maximal at a dose o f 50 mg/kg. Caffeine increased the plasma concentration of corticosterone, but it had no effect on the brain or plasma concentrations of 3 alpha,21-di hydroxy-5 alpha-pregnan-20-one and dehydroepiandrosterone. Moreover, the br ain and plasma concentrations of pregnenolone, progesterone, and allopregna nolone were not affected by caffeine in adrenalectomized-orchiectomized rat s. These results suggest that neuroactive steroids may modulate the stimula nt and anxiogenic effects of caffeine. (C) 2000 Elsevier Science Inc.