ROLE OF GABA(A) RECEPTORS IN SLEEP REGULATION - DIFFERENTIAL-EFFECTS OF MUSCIMOL AND MIDAZOLAM ON SLEEP IN RATS

To assess the influence of the gamma-aminobutyric acid (GABA)(A) recep tor on sleep and sleep EEG, rats were injected intraperitoneally with vehicle, two doses of muscimol (0.2 and 0.4 mg/kg), a selective GABA(A ) agonist, and midazolam (3 mg/kg), a benzodiazepine-GABAA agonist. EE G and EMG recordings were made for 6 or 8 hours. Muscimol dose-depende ntly increased the amount of nonrapid eye movement sleep (nonREMS) and REMS. The higher dose of muscimol enhanced EEG activity over almost t he entire frequency range (0.5-25 Hz), including delta (0.5-4 Hz) and sigma (11-16 Hz) activity, within nonREMS and in the frequencies over 10 Hz within REMS. Midazolam also increased the amount of nonREMS. How ever, most of the other effects of midazolam contrasted the effects of muscimol: midazolam decreased REMS, reduced low frequency (less than or equal to 11 Hz) EEG activity within nonREMS, and enhanced the activ ity in higher frequencies during both nonREMS and REMS. These data dem onstrate the involvement of GABA(A) receptors in the regulation of sle ep-wake behavior as well as in the generation of spindles and delta wa ves during nonREMS. The effects of these two GABA(A) agonists indicate that activation of different binding sites on the GABA(A) receptor co mplex differentially affect sleep states and sleep EEG.