Effects of methoxamine, and alpha-1 adrenoceptor agonist, and prazosin, an alpha-1 antagonist, on the stages of the sleep-waking cycle in the cat.

In these experiments the effects of alpha 1-adrenoceptor agonism and antagonism were studied on the stages of the sleep-waking cycle of the cat, in order to determine optimal levels of alpha 1-adrenergic transmission for these stages. Polygraphic 16-h recordings showed that prazosin, an alpha 1-adrenoceptor antagonist, at 1 mg/kg i.p., increased paradoxical sleep (PS) time from 15.3% to 26.4% (p less than 0.001) of total time, and the number of PS episodes from 30.4 to 43.6 (p less than 0.001). The effect was prompt, reaching a maximum during the first 4 h with a shortening of PS latency from 40.4 min to 11.0 min (p less than 0.001). Prazosin at doses of 0.5 and 3.0 though not at 10.0 mg/kg also slightly, but significantly, increased PS. Methoxamine, and alpha 1-adrenoceptor agonist, at doses of 0.5 and 3.0 mg/kg, increased aroused waking time (low voltage mixed frequency EEG) during the first 4 h from 23.5% to 33.3% (p less than 0.05) and to 50.3% (p less than 0.01), and decreased PS. Prazosin potentiated dose-dependently clonidine-induced drowsiness ( hypersynchronized 4-8 Hz EEG), whereas the decrease in deep slow wave sleep and PS were potentiated only at the largest dose of it. These results indicate that moderate inhibition of cerebral alpha 1-adrenergic transmission facilitates paradoxical sleep in the cat. Furthermore, they suggest that the level of cerebral alpha 1-adrenergic transmission is high during aroused waking and low during drowsy waking.