Elimination of REM sleep rebound in rats by alpha-adrenoreceptor blockers, phentolamine and phenoxybenzamine.

Two alpha-adrenoreceptor blocking agents, phentolamine (5 mg/kg, IP) and phenoxybenzamine (10 mg/kg IP) were administered to rats deprived of rapid eye movement (REM) sleep for 24 hours to test the hypothesis that reduced noradrenergic transmission may abolish REM sleep rebound. The hypothesis was based on results from our previous studies which showed that administration to rats of diethyldithiocarbamate (DDC), a dopamine beta hydroxylase inhibitor, decreased the concentration of brain norepinephrine and reduced REM sleep permanently without the subsequent appearance of REM sleep rebound. Present results show that administration of both alpha-adrenoreceptor blockers abolished REM sleep rebound. At the time of maximum reduction of REM sleep, the concentration of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MOPEGSO4), a final product of norepinephrine metabolism in the brain, was found increased in the whole brains of rats suggesting that the selected doses of the drugs were sufficient to produce effective central alpha-adrenergic receptor blockade. These data indicate that the action of both alpha-adrenoreceptor blocking agents in noradrenergic system was paralleled by the permanent loss of REM sleep and support the hypothesis implicating reduced noradrenergic transmission in elimination of REM sleep rebound.