Effects of Methoxamine and a-Adrenoceptor Antagonists, Prazosin and Yohimbine, on the Sleep-Wake Cycle of the Rat

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Abstract
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 α1-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 α2-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 α1- or blocking of α2-adrenoceptors appears to decrease sleep and increase W Further, blocking of α1-adrenoceptors decreases REMS. Rapid eye movement sleep depression by the α1-agonist or the α1-antagonist is tentatively ascribed to a critical change in noradrenergic transmission in the brain.

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