The Journal of Neurophysiology Vol. 77 No. 3 March 1997, pp. 1624-1629
Copyright ©1997 The American Physiological Society

Muscimol and Midazolam Do Not Potentiate Each Other's Effects on Sleep EEG in the Rat

Marike Lancel, Johannes Faulhaber, Thomas Schiffelholz, Stefan Mathias, and Rudolf A. Deisz

Max-Planck Institute of Psychiatry, Clinical Institute, 80804 Munich, Germany

Lancel, Marike, Johannes Faulhaber, Thomas Schiffelholz, Stefan Mathias, and Rudolf A. Deisz. Muscimol and midazolam do not potentiate each other's effects on sleep EEG in the rat. J. Neurophysiol. 77: 1624-1629, 1997. The interaction of a -aminobutyric acid-A (GABA_A) receptor agonist and a benzodiazepine-type modulator of GABA_A receptors on sleep was investigated. Low doses of muscimol (0.3 mg/kg) and the benzodiazepine midazolam (1.5 mg/kg) were administered alone and incombination, in random order, to eight rats. All injections were given intraperitoneally at light onset. Electroencephalogram (EEG) and electromyogram were recorded during the first 6 h post injection. Compared with vehicle, muscimol hardly affected the time spent in non-rapid eye movement sleep (non-REMS) and REMS, but significantly enhanced EEG activity in the frequency range between 2 and 6 Hz during non-REMS. Midazolam significantly increased the time spent in non-REMS, reduced EEG activity at frequencies <12 Hz, and elevated EEG activity in most higher frequencies during this state. The combined administration of muscimol and midazolam affected non-REMS-specific EEG activity in an unexpected fashion: the effects were intermediate between those of muscimol and midazolam. These results indicate that muscimol and midazolam have dissimilar effects on EEG within non-REMS and demonstrate that midazolam does not augment but attenuates the muscimol-induced changes in sleep EEG. Our 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 application of agonists and agonistic modulators of GABA_A receptors causes differential net effects on sleep parameters.

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