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ANESTHETIC PHARMACOLOGY

Alpha-2 Adrenoceptor Activity Affects Propofol-Induced Sleep Time

Department of Anesthesiology, University of Hirosaki School of Medicine, Japan

Address correspondence and reprint requests to Tetsuya Kushikata, MD, Department of Anesthesiology, University of Hirosaki School of Medicine, 5 Zaifu-cho, Hirosaki, Japan. Address e-mail to tkush{at}df6.so-net.ne.jp

₂ Adrenoceptor activity is involved in the mechanism of anesthesia. Clonidine, a ₂ adrenoceptor agonist, and yohimbine, a ₂ adrenoceptor antagonist, increase and decrease barbiturate-induced sleep times. In this study, we examined the effects of these drugs on propofol-induced sleep time. One-hundred-eighteen male Wistar rats weighing 320–400 g were used. Rats received saline, yohimbine (1, 0.1, or 0 mg/kg), or clonidine (300, 30, 3, or 0 µg/kg) intraperitoneally followed by 60 mg/kg of propofol in various combinations. In two series of experiments, either sleep time or prefrontal cortex norepinephrine release (microdialysis) was measured. One milligram/kilogram of yohimbine decreased propofol-induced sleep time to approximately 70% of control, and this was accompanied by an increase in perfusate norepinephrine of approximately 240% of control. Clonidine increased sleep time approximately 260% (300 µg/kg) and approximately 170% (30 µg/kg), and this was accompanied by a decrease (approximately 60% in both doses) in perfusate norepinephrine. In the present study, we show that the ₂ antagonist, yohimbine, decreased and the ₂ agonist, clonidine, increased propofol-induced sleep times. These changes were essentially mirrored in both groups by changes in norepinephrine release in the prefrontal cortex.

IMPLICATIONS: Central ₂ adrenoceptor is thought to be involved in several IV anesthetics-induced sleep. In this study, activation of the receptor increased the propofol-induced sleep time, whereas its inhibition decreased the sleep time. The results provide further evidence that the ₂ receptor is a good tool to elucidate the mechanism of anesthetics-induced sleep.

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