MODULATION OF FOREBRAIN ELECTROENCEPHALOGRAPHIC ACTIVITY IN HALOTHANE-ANESTHETIZED RAT VIA ACTIONS OF NORADRENERGIC BETA-RECEPTORS WITHIN THE MEDIAL SEPTAL REGION

The locus coeruleus (LC)-noradrenergic system modulates forebrain elec troencephalographic (EEG) activity in halothane-anesthetized rat. For example, unilateral enhancement of LC neuronal activity increases cort ical EEG (ECoG) and hippocampal EEG (HEEG) indices of arousal bilatera lly (Berridge and Foote, 1991). Conversely, bilateral suppression of L G discharge activity increases EEG measures of sedation (Berridge et a l., 1993b). The EEG-activating effects of LC stimulation appear to inv olve noradrenergic beta-receptors (Berridge and Foote, 1991). Two cand idate sites at which LG efferents could influence ECoG and HEEG are th e medial septum/vertical limb of the diagonal band of Broca (MS) and t he substantia innominata/nucleus basalis of Meynert (SI). To determine whether norepinephrine mediates such actions within either of these r egions, the EEG effects of small infusions of a beta-agonist or antago nist into MS or SI were examined in halothane-anesthetized rat. Unilat eral infusions (150 nl) of the beta-agonist isoproterenol (ISO)(3.75 m u g, 17 nmol) into MS, but not SI (150-450 nl), elicited robust bilate ral activation of ECoG and HEEG. infusions of glutamate (0.5 mu g, 3.0 nmol) into either MS or SI elicited bilateral ECoG and HEEG activatio n. Neither vehicle infusions into MS nor infusions of ISO into regions adjacent to MS altered forebrain EEG activity. Bilateral, but not uni lateral, MS infusions of the beta-antagonist timolol (3.75 mu g, 8.7 n mol) decreased EEG indices of arousal in the lightly anesthetized prep aration. Power spectral analyses provided quantitative confirmation of these qualitative observations. These results indicate that under the se experimental conditions, noradrenergic efferents, presumably arisin g from LC, modulate forebrain EEG state via actions at beta-receptors located within MS. The results presented in the accompanying report ex tend these observations to the unanesthetized preparation and incorpor ate additional measures of behavioral state.