Sleep EEG changes after zolpidem in mice

Zolpidem is a widely used hypnotic that binds preferentially to alpha1GABAA receptors. We determined the role of these receptors in the effects of zolpidem on sleep in mutant mice carrying zolpidem-insensitive alpha1GABAA receptors and wild-type controls. Sleep was promoted by zolpidem in both genotypes. In wild-type mice non-REM sleep EEG power was markedly reduced in a broad frequency band >5 or 9 Hz after 5 and 10 mg/kg zolpidem, respectively. In mutants a power reduction appeared at the highest dose only, and was restricted to some low frequencies and the 9-10 Hz bin. We conclude that the effects of zolpidem on the sleep EEG in mice are distinct from the changes typically induced by benzodiazepines, and are primarily mediated by alpha1GABAA receptors.