Pii: S0306-4522(00)00215-3

The locus coeruleus–noradrenergic system exerts an activating influence on forebrain neuronal and behavioral activity states. For example, in the anesthetized rat, unilateral locus coeruleus stimulation elicits bilateral activation of forebrain electroencephalographic activity. Pretreatment with a noradrenergic b-antagonist blocks this effect, suggesting that b-receptors play a critical role in locus coeruleus-dependent activation of the forebrain. Consistent with this, stimulation of b-receptors located in certain basal forebrain structures evokes sustained periods of alert waking in the unanesthetized rat. Similar forebrain and behavioral activating effects are observed with a1-receptor stimulation within these basal forebrain regions. To assess the extent to which a1and b-receptors contribute to the maintenance of behavioral and forebrain activation, we examined the electroencephalographic and behavioral effects of a1-, band combined a1/b-receptor blockade in the unanesthetized rat. Rats were treated individually or in combination with either varying doses of the a1-antagonist, prazosin (intraperitoneally), and/or the b-antagonist, timolol (intracerebroventricularly). Thirty minutes following treatment, animals were placed in a mildlyarousing novel environment, which has been demonstrated previously to elicit activation of central noradrenergic systems and sustained waking in vehicle-treated controls. Behavior and electroencephalographic activity were recorded and later scored. Electroencephalographic activity was analysed using power spectrum analysis. The following were observed: (i) b-receptor blockade alone does not alter behavioral or electroencephalographic indices of alert waking; (ii) a1-receptor blockade alone increases high-voltage spindle activity in cortical electroencephalographic activity that was associated with decreased behavioral activity; (iii) combined a1and b-receptor blockade elicits a substantial increase in slow-wave activity (0.33–2.0 Hz), also in association with decreased behavioral activity. All of these effects were dependent on the dose administered and time following initiation of testing. These results indicate that the combined actions of a1and b-receptors exert distinct and synergistic actions on cortical neuronal activity patterns that are essential elements of alert waking. q 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.