Summary: A study was carried out on the effects of methoxamine, prazosin, and yohimbine on the sleep-wake cycle in rats prepared for chronic sleep recordings. Methoxamine (4-8 mg/kg), an al-adrenoceptor agonist, induced a doserelated increase in wakefulness (W) and a decrease in slow-wave sleep (SWS) and REM sleep (REMS). Prazosin (0.125-1 mg/kg), which selectively blocks aladrenoceptors, modified only slightly the amount of time spent in Wand SWS, and consistently decreased REMS values. Prazosin (0.5 mg/kg) reversed the effects of methoxamine, decreasing Wand increasing sleep. Yohimbine (3 mg/kg), which blocks a2-adrenoceptors, augmented Wand diminished sleep. Methoxamine (4 mg/kg) in animals pretreated with yohimbine (3 mg/kg) induced a further decrease of SWS and REMS and an increase of W Thus, pharmacological activation of al-or blocking of a2-adrenoceptors appears to decrease sleep and increase W Further, blocking of al-adrenoceptors decreases REMS. Rapid eye movement sleep depression by the aI-agonist or the aI-antagonist is tentatively ascribed to a critical change in noradrenergic transmission in the brain. Key Words:Waking-Sleep--Methoxamine-Prazosin-Yohimbine.Intraventricular administration of adrenergic agonists of al-and a2-adrenoceptors (norepinephrine, epinephrine) produces a state of prolonged wakefulness (W) (I). Compounds that indirectly activate both noradrenergic and dopaminergic receptors (amphetamine, methylphenidate) also profoundly affect the sleep-wake cycle. As a result, slow-wave sleep (SWS) and REM sleep (REMS) are decreased and W is increased (2,3). Several other compounds including methoxamine also induce an increase of waking electroencephalography (EEG), which has been related to selective activation of al-adrenoceptors (4).The present study quantifies the effect of methoxamine on the sleep-wake cycle of the rat and attempts to ascertain the role of al-and a2-receptors in the methoxamine-induced disruption of the sleep-wake cycle. The effects of methoxamine were assessed after pretreatment with either prazosin, which selectively blocks al-adrenoceptors, or yohimbine, which behaves as an antagonist of a2-adrenoceptors.

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