Pharmacology Biochemist~ & Behavior, Vol. 13, pp. 51-55. Printed in the U.S.A. Elimination of REM Sleep Rebound in Rats by c -Adrenoreceptor Blockers, Phentolamine and Phenoxybenzamine MIODRAG RADULOVACKI, WALTER J. WOJCIK, CASIMIR FORNAL AND ROBERT MILETICH Department of Pharmacology, College of Medicine, University of lllinois at the Medical Center Chicago, IL 60680 Received 8 March 1980 RADULOVACK1, M., W. J. WOJCIK, C. FORNAL AND R. MILETICH. Eliminationof REM sleep rebound in rats by c~-adrenoreceptor blockers, phentolamine and phenoxybenzamine. PHARMAC. BIOCHEM. BEHAV. 13(1) 51-55, 1980.--Two c~-adrenoreceptor blocking agents, phentolamine (5 mg/kg, IP) and phenoxybenzamine (10 mg/~g 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 h~,pothesis 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 appear- ance of REM sleep rebound. Present results show that administration of both a-adrenoreceptor blockers abolished REM sleep rebound. At the time of maximum reduction of REM sleep, the concentration of 3-methoxy-4-hydroxyphenylethyl- eneglycol 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 a-adrenergic receptor blockade. These data indicate that the action of both a-adrenoreceptor blocking agents in noradrenergic system was paralleled by the permanent loss of REM sleep and support the hypothesis implicating reduced noradrenergic trans- mission in elimination of REM sleep rebound. Phentolamine Phenoxybenzamine Elimination of REM sleep rebound THE aim of this work was to test the hypothesis that reduced noradrenergic transmission may abolish rapid eye movement (REM) sleep without producing subsequent REM sleep re- bound. The hypothesis was based on results from our previ- ous studies which showed that administration to rats of di- ethyldithiocarbamate (DDC), a dopamine (DA) beta hy- droxylase inhibitor [4], decreased the concentration of nor- epinephrine (NE) in specific brain structures [25] and re- duced REM sleep permanently without the subsequent ap- pearance of REM sleep rebound [11]. However, since the inhibition of DA beta hydroxylase resulted in a decrease of brain NE content, it was not certain whether this reduction actually affected noradrenergic transmission. In attempting to reduce noradrenergic transmission by a different approach and to examine its effect on REM sleep rebound we used a-adrenoreceptor blockers in a situation in which REM "pressure" is increased by a selective REM deprivation method [7,16] and as a result REM sleep appears in a greater amount. We administered two a-adrenoreceptor blockers, phentolamine [18] and phenoxybenzamine [19] to rats selectively deprived of REM sleep. Our results show that administration of both agents abolished REM sleep re- bound and, in the case of phenoxybenzamine, REM sleep was reduced to levels below that seen in normal rats. METHOD Implantation of Electrodes, REM Sleep Deprivation and Polygraphic Recording Adult male Sprague-Dawley rats (400-500 g) were im- planted with cortical and dorsal neck muscle electrodes for polygraphic recording. One week after surgery animals were selectively deprived of REM sleep for twenty-four hours by the "flower pot" method where animals are placed on plat- forms surrounded by water [7]. The method is based on the phenomenon that during REM sleep there is a loss of muscle tone which causes the animals to fall off the platforms. The animals awake at the onset of each REM episode and thus are deprived of REM sleep. To standardize the degree of REM deprivation (RD) rats were placed on circular plat- forms whose surface area corresponded to their body weight [6,16]. A surface area to animal weight ratio of 14 cm2/100 g was used. After 24 hr of RD, animals were divided in three groups. The animals in the first group received phentolamine hydrochloride (5 mg/kg, IP), those in the second group re- ceived phenoxybenzamine hydrochloride (10 mg/kg, IP) and the rats in the third, control, group received the drug vehicle, propylene glycol (0.5 ml/kg, IP). After the drugs were ad- ministered, EEG and EMG were continously monitored for Copyright © 1980 ANKHO International Inc.--0091-3057/80/070051-05501.00/0