Effects of methoxamine and alpha-adrenoceptor antagonists, prazosin and yohimbine, on the sleep-wake cycle of the rat.
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 alpha 1-adrenoceptor agonist, induced a dose-related 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 alpha 1-adrenoceptors, modified only slightly the amount of time spent in W and SWS, and consistently decreased REMS values. Prazosin (0.5 mg/kg) reversed the effects of methoxamine, decreasing W and increasing sleep. Yohimbine (3 mg/kg), which blocks alpha 2-adrenoceptors, augmented W and 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 alpha 1- or blocking of alpha 2-adrenoceptors appears to decrease sleep and increase W. Further, blocking of alpha 1-adrenoceptors decreases REMS. Rapid eye movement sleep depression by the alpha 1-agonist or the alpha 1-antagonist is tentatively ascribed to a critical change in noradrenergic transmission in the brain.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology*
D011799:Quinazolines; D015016:Yohimbine; D008729:Methoxamine; D011224:Prazosin