Noradrenergic and Dopaminergic Regulation of Arousal/Waking.
The catecholamine neurotransmitters are among a number of systems that originate within the brainstem and project widely throughout the central nervous system. These transmitters are thought to play a prominent role in reward, addiction, and various psychiatric/behavioral disorders. The primary source of brain norepinephrine is the locus coeruleus, a small collection of neurons located within the pontine brainstem. The fact that these neurons display state-dependent activity, with greater activity observed in waking than in sleep, has long suggested that these neurons participate in the induction of the alert waking state. In a series of studies, our laboratory has investigated the extent to which the locus coeruleus-noradrenergic system modulates behavioral state.		This work demonstrated robust wake-promoting actions of this neurotransmitter system and has identified regions within the basal forebrain where norepinephrine acts to promote alert waking. Current work examines the receptor subtypes involved in these actions and the state-modulatory actions of norepinephrine outside the basal forebrain, including within neocortex. Additionally, evidence suggests that dopamine may also exert arousal-enhancing actions. Current work begins to assess the extent to which dopamine modulates behavioral state and identify the receptor mechanisms and circuitry that underlie such actions.
Related Publications: Berridge, CW, Arnsten, AFT, and Foote, SL. (1993) Noradrenergic modulation of cognitive function: clinical implications of anatomical, electrophysiological, and behavioral studies in animal models. Psychological Medicine, 23:557-564. (Solicited Editorial). Berridge, CW and Foote, SL. (1991) Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus. Journal of Neuroscience, 11:3135-3145. Berridge, CW, Page, M, Valentino, RJ, and Foote, SL. (1993) Effects of locus coeruleus inactivation on forebrain electroencephalogragaphic activity. Neuroscience, 55:381-393. Berridge, CW, Bolen, SJ, Manley, MS and Foote, SL. (1996) Modulation of forebrain electroencephalographic (EEG).activity in the halothane-anesthetized rat via actions of noradrenergic b-receptors located within the medial septal region of the basal forebrain. Journal of Neuroscience, 16:7010-7020. Berridge, CW and Foote, SL. (1996) Enhancement of behavioral, electroencephalographic (EEG), and electromyographic (EMG).indices of waking following stimulation of noradrenergic b-receptors located within the medial septal region of the basal forebrain in the unanesthetized rat. Journal of Neuroscience, 16:6999-7009. Berridge, CW, Stratford, T, Foote, SL, and Kelley, AE. (1997) Localization of DBH-like immunoreactive fibers within the shell of the nucleus accumbens. Synapse, 27, 230-241. Berridge, CW and Abercrombie, ED. (1999) Relationship between locus coeruleus neuronal discharge rate and rates of norepinephrine efflux in cortex. Neuroscience, 93:1263-1270. Berridge, CW and Wifler, K. (2000) Contrasting effects in anesthetized and unanesthetized rat of noradrenergic b-receptor blockade within the medial septal area on forebrain EEG and behavioral activity state. Neuroscience, 97:543-552. Berridge, CW, España, RA. (2000) Synergistic sedative effects of noradrenergic alpha(1)- and beta-receptor blockade on forebrain electroencephalographic and behavioral indices. Neuroscience, 99, 495-505. Berridge, CW and O’Neill, J. (2001) Differential Sensitivity to the Wake-Promoting Actions of Norepinephrine Within the Medial Preoptic Area and the Substantia Innominata. Behavioral Neuroscience, 115:165-174. Berridge, CW. (2001) Attention- and Arousal-Related Actions of the Locus Coeruleus-Noradrenergic System: Potential Target in the Therapeutic Actions of Amphetamine-Like Stimulants. In: The Neuropharmacology of Psychostimulant Drugs: Implications for ADHD, Solanto, M, Arnsten AFT, Castalleno, X eds. pps. 158-184. Berridge CW. Pharmacological Investigations of Amphetamine-Induced Arousal: Noradrenergic Mechanisms. In: Methods in Drug Abuse Research: Cellular and Circuit Level Analysis, B. Waterhouse, ed. CRC Press, Boca Raton, in press. back to list of Current Research projects

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