Depressant effect of androgens on the cat brain electrical activity and its antagonism by ruthenium red

Electroencephalographic synchronization and a fall in the multiunit activity was observed in the mesencephalic reticular formation, ventromedial hypothalamus and dorsal hippocampus following intravenous administration of some 5 alpha and 5 beta-reduced testosterone derivatives. The most potent compounds were androsterone and androstanediol which have the 3 alpha-hydroxy-5 alpha ring A configuration. Steroids with 5 beta reduction, i.e. 5 beta-dihydrotestosterone, etiocholanolone and epi-etiocholanolone, at high doses produced the inhibitory effect. Testosterone and its closer 5 alpha metabolites (5 alpha-dihydrotestosterone and 5 alpha-androstanedione) were ineffective. The depressive effect of androsterone on neurones was antagonized by the intraventricular injection of ruthenium red. On the other hand, the convulsant effect of ruthenium red was prevented or diminished by the action of androsterone. These findings support the hypothesis that testosterone metabolites reduced either at 5 alpha or 5 beta position can act in the brain at a membrane level and raise the possibility that testosterone may be a prehormone in the regulation of excitability in some brain functions.