Actions of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone on single neurones of the mesencephalic reticular formation in the rat

The effects of microinjections of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone (3 alpha-THDOC) on single neurones of the mesencephalic reticular formation (MRF) were investigated in rats anaesthetized with urethan. Microinjections of approximately 100 nl of 0.5-2 microM 3 alpha-THDOC inhibited firing of 105 of 112 neurones (94%). Microinjections of approximately 100 nl of 100-250 nM of 3 alpha-THDOC did not alter neuronal activity, but in 52 of 68 cases (76%) it potentiated the inhibitory action of microiontophoretically applied gamma-aminobutyric acid (GABA). The 3 beta-isomer of tetrahydrodeoxycorticosterone did not elicit any changes in neuronal firing. The effects of 3 alpha-THDOC were reversibly antagonized by microiontophoretically applied bicuculline. This 'in vivo' study supports the hypothesis that 3 alpha-THDOC may function as endogenous modulator of GABAA-mediated inhibition in various physiopathological conditions.