Changes in multiunit activity and EEG induced by the administration of natural progestins to flaxedil immobilized...

The effects of progesterone (P) and 7 of its metabolites on the EEG and multiunit activity (MUA) of various limbic structures were studied in flaxedil immobilized cats. Most progestins inhibited the MUA of the mesencephalic reticular formation, hippocampus and hypothalamus and induced cortical EEG synchronization. MUA changes in the mesencephalic reticular formation frequently preceded EEG synchronization. Progestins reduced in the 5 beta postition (pregnanolone, epipregnanolone and pregnanedion) inhibited neuronal discharge and synchronized EEG activity with shorter latencies and in lower doses than those reduced in the 5 alpha position (allopregnanolone and allopregnanedion). Progestins having the delta 4,3-keto structure (P, 20 alpha-hydroxy pregnenone, 20 beta-hydroxy pregnenone) induced electrophysiological changes with prolonged latencies and in doses significantly higher than ring A reduced progestins. Administration of epipregnanolone to "cerveau isole" preparations depressed neuronal firing in those structures located rostral to the level of the brain stem transection (hypothalamus, hippocampus), but failed to increase the already synchronized cortical activity. These results suggest that: a, ring A reduction increases the capacity of P and other delta 4,3-keto progestins to inhibit neuronal discharge in certain brain areas and b, changes in neuronal firing induced by progestins are not necessarily mediated through the cat brain stem reticular formation.