Alpha-2 Adrenoceptor Activity Affects Propofol-Induced Sleep Time

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Abstract
α2 Adrenoceptor activity is involved in the mechanism of anesthesia. Clonidine, a α2 adrenoceptor agonist, and yohimbine, a α2 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 α2 antagonist, yohimbine, decreased and the α2 agonist, clonidine, increased propofol-induced sleep times. These changes were essentially mirrored in both groups by changes in norepinephrine release in the prefrontal cortex.