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) receptor 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. EEG and EMG recordings were made for 6 or 8 hours. Muscimol dose-dependently increased the amount of nonrapid eye movement sleep (nonREMS) and REMS. The higher dose of muscimol enhanced EEG activity over almost the 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. However, 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 activity in higher frequencies during both nonREMS and REMS. These data demonstrate the involvement of GABA(A) receptors in the regulation of sleep-wake behavior as well as in the generation of spindles and delta waves during nonREMS. The effects of these two GABA(A) agonists indicate that activation of different binding sites on the GABA(A) receptor complex differentially affect sleep states and sleep EEG.