Contrasting effects of noradrenergic beta-receptor blockade within the medial septal area on forebrain electroencephalographic and behavioral activity state in anesthetized and unanesthetized rat

Abstract

The locus coeruleus-noradrenergic system participates in the modulation of behavioral state. Previous studies demonstrated that beta-receptors located within the general region encompassing the medial septum/vertical limb of the diagonal band of Broca (medial septal area) exert arousal-enhancing actions in both anesthetized and unanesthetized animals. These studies also demonstrated that, under conditions of limited locus coeruleus discharge rates, blockade of beta-receptors within this region decreased forebrain electroencephalographic indices of arousal. The current studies assess the extent to which medial septal area beta-receptors contribute to the maintenance of electroencephalographic and/or behavioral indices of arousal, under conditions associated with elevated locus coeruleus discharge rates. In the halothane-anesthetized rat, bilateral, but not unilateral, blockade of beta-receptors within this area prevented forebrain (cortical and hippocampal) electroencephalographic activation elicited by activation of locus coeruleus neurons. Placement of beta-antagonist immediately adjacent to the medial septal area had no effect on locus coeruleus-dependent cortical and hippocampal electroencephalographic activation. In contrast, in unanesthetized rat, bilateral pretreatment of the medial septal area did not alter either electroencephalographic or behavioral measures in animals tested in an arousal-enhancing, brightly-lit novel environment, which has been demonstrated to elicit an activation of the locus coeruleus-noradrenergic system. The results obtained in anesthetized animals are consistent with previous studies demonstrating potent modulatory actions of noradrenergic systems on actions of general anesthetics, and suggest that beta-receptors may be an appropriate target for pharmacological adjuncts to general anesthetics. In contrast to that observed in anesthetized animals, medial septal beta-receptors alone do not contribute significantly to the maintenance of an activated forebrain in unanesthetized animals. It is presumed that actions of other noradrenergic receptors and/or other neurotransmitter systems located within or outside the medial septal area make the arousal-modulating actions of medial septal area beta-receptors redundant, in the unanesthetized, alert animal.