Modulation of Forebrain Electroencephalographic Activity in Halothane-Anesthetized Rat via Actions of Noradrenergic β-Receptors within the Medial Septal Region

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Abstract
The locus coeruleus (LC)–noradrenergic system modulates forebrain electroencephalographic (EEG) activity in halothane-anesthetized rat. For example, unilateral enhancement of LC neuronal activity increases cortical EEG (ECoG) and hippocampal EEG (HEEG) indices of arousal bilaterally (Berridge and Foote, 1991). Conversely, bilateral suppression of LC discharge activity increases EEG measures of sedation (Berridge et al., 1993b). The EEG-activating effects of LC stimulation appear to involve noradrenergic β-receptors (Berridge and Foote, 1991).Two candidate sites at which LC efferents could influence ECoG and HEEG are the medial septum/vertical limb of the diagonal band of Broca (MS) and the substantia innominata/nucleus basalis of Meynert (SI). To determine whether norepinephrine mediates such actions within either of these regions, the EEG effects of small infusions of a β-agonist or antagonist into MS or SI were examined in halothane-anesthetized rat. Unilateral infusions (150 nl) of the β-agonist isoproterenol (ISO) (3.75 μg, 17 nmol) into MS, but not SI (150–450 nl), elicited robust bilateral activation of ECoG and HEEG. Infusions of glutamate (0.5 μg, 3.0 nmol) into either MS or SI elicited bilateral ECoG and HEEG activation. Neither vehicle infusions into MS nor infusions of ISO into regions adjacent to MS altered forebrain EEG activity. Bilateral, but not unilateral, MS infusions of the β-antagonist timolol (3.75 μg, 8.7 nmol) decreased EEG indices of arousal in the lightly anesthetized preparation. Power spectral analyses provided quantitative confirmation of these qualitative observations.These results indicate that under these experimental conditions, noradrenergic efferents, presumably arising from LC, modulate forebrain EEG state via actions at β-receptors located within MS. The results presented in the accompanying report extend these observations to the unanesthetized preparation and incorporate additional measures of behavioral state.