MUSCIMOL AND MIDAZOLAM DO NOT POTENTIATE EACH OTHERS EFFECTS ON SLEEPEEG IN THE RAT

The interaction of a gamma-aminobutyric acid-A (GABA(A)) receptor agon ist and a benzodiazepine-type modulator of GABA(A) receptors on sleep was investigated. Low doses of muscimol (0.3 mg/kg) and the benzodiaze pine midazolam (1.5 mg/kg) were administered alone and in combination, in random order, to eight rats. All injections were given intraperito neally at light onset. Electroencephalogram (EEG) and electromyogram w ere recorded during the first 6 h post injection. Compared with vehicl e, muscimol hardly affected the time spent in non-rapid eye movement s leep (non-REMS) and REMS, but significantly enhanced EEG activity in t he frequency range between 2 and 6 Hz during non-REMS. Midazolam signi ficantly increased the time spent in non-REMS, reduced EEG activity at frequencies <12 Hz, and elevated EEG activity in most higher frequenc ies during this state. The combined administration of muscimol and mid azolam affected non-REMS-specific EEG activity in an unexpected fashio n: the effects were intermediate between those of muscimol and midazol am. These results indicate that muscimol and midazolam have dissimilar effects on EEG within non-REMS and demonstrate that midazolam does no t augment but attenuates the muscimol-induced changes in sleep EEG. Ou r data are at variance with established mechanisms, according to which agonistic modulators would have similar effects and should potentiate the effects of GABA(A) agonists. The present data suggest that applic ation of agonists and agonistic modulators of GABA(A) receptors causes differential net effects on sleep parameters.