Potentiation of the depression by adenosine of rat cerebral cortical neurones by progestational agents

Abstract

The effects of four progestational agents pregnenolone sulphate, cyproterone acetate, norethindrone acetate and progesterone, on adenosine‐evoked depression of the firing of rat cerebral cortical neurones have been studied. When applied iontophoretically, pregnenolone sulphate, cyproterone, and norethindrone enhanced the actions of iontophoretically applied adenosine and failed to potentiate the depressant effects of adenosine 5′‐N‐ethylcarboxamide and γ‐aminobutyric acid. Cyproterone acetate (50 μg kg−1) and progesterone (200 μg kg−1) administered intravenously enhanced the depressant actions of iontophoretically applied adenosine. When applied by large currents, cyproterone, and less frequently norethindrone, depressed the firing of cerebral cortical neurones. The depressant effects of cyproterone were antagonized by caffeine. Pregnenolone sulphate tended to excite cortical neurones but neither this action, nor its potentiation of adenosine were reproduced by application of sulphate ions. It is hypothesized that some of the psychotropic actions of progestational agents may involve an enhancement of ‘purinergic’ tone in the central nervous system. 1986 British Pharmacological Society