The GABA(A) receptor antagonist picrotoxin attenuates most sleep changes induced by progesterone

Progesterone has been shown to exert benzodiazepine-like effects on sleep, which suggests that they are mediated by an agonistic modulation of GABA(A) receptor functioning. To assess the involvement of GABA(A) receptors, we i nvestigated the sleep responses to one dose of the GABA(A) antagonist picro toxin (1.5 mg/kg) and progesterone (90 mg/kg), administered IP to eight rat s alone and in combination, during the first 4 post-injection hours. Compar ed with vehicle, picrotoxin significantly delayed the latency to non-rapid eye movement sleep (non-REMS) and thereby decreased all sleep states, but b arely affected the EEG activity within non-REMS. Progesterone significantly shortened non-REMS latency, increased pre-REMS, depressed low-frequency EE G activity (less than or equal to 8 Hz) and augmented EEG activity in the h igher frequencies within non-REMS. Except for the changes in high-frequency EEG activity, picrotoxin attenuated all effects of progesterone. These fin dings support the notion that GABA(A) receptors play an important role in t he sleep effects of progesterone.