Enhancement of Behavioral and Electroencephalographic Indices of Waking following Stimulation of Noradrenergic β-Receptors within the Medial Septal Region of the Basal Forebrain

Previous studies in halothane-anesthetized rat documented potent electroencephalographic (EEG) modulatory actions of the locus coeruleus (LC) noradrenergic system, with LC neuronal activity causally related to the maintenance of EEG activity patterns associated with enhanced arousal/alertness. Recent studies, also in halothane-anesthetized rat, demonstrated that the region of the basal forebrain encompassing the medial septum/vertical limb of the diagonal band of Broca (MS) is a site at which noradrenergic efferents act to influence EEG state via actions at beta-receptors. These and other observations are consistent with the hypothesis that the LC noradrenergic system participates in the modulation of behavioral state. However, the degree to which this system modulates EEG state in the absence of anesthesia and to what extent such actions are accompanied by behavioral modulatory actions remain to be determined. The current studies examined whether small infusions of isoproterenol (ISO), a beta-adrenergic agonist, into MS alter behavioral, EEG, and electromyographic (EMG) measures of sleep and waking in the resting, undisturbed rat. These infusions resulted in a significant increase in time spent awake, defined by both behavioral and EEG/EMG measures, and in the nearly complete suppression of REM sleep. EEG/EMG responses either coincided with or preceded behavioral responses by 10-320 sec. The pattern of behavioral responses observed following MS-ISO infusions was qualitatively similar to that associated with normal waking. Infusions of vehicle into MS or ISO into sites adjacent to MS did not elicit consistent alterations in behavioral state. These results suggest that the LC noradrenergic system exerts potent behavioral and EEG-activating effects via actions of norepinephrine at beta-receptors located within MS.