Neural Bases of Amphetamine-Induced Arousal.
Amphetamine-like stimulants are a widely abused class of drugs. In addition to their abuse potential, these drugs are also used in low doses clinically in the treatment of narcolepsy and attention-deficit hyperactivity disorder (ADHD). Although these drugs elicit a variety of behavioral effects, all of these are superimposed upon the robust arousal-enhancing actions of these drugs. The arousal-enhancing actions of these drugs contribute to their widespread use and abuse. Moreover, the clinical actions of these drugs, are much more closely associated with their arousal-enhancing actions than with their locomotor-activating and reinforcing actions. Surprisingly, despite intense examination of the neurobiology of this class of drug over the past one-half century, little is known concerning the mechanisms through which amphetamines exert their arousal-enhancing actions.		Amphetamines increase synaptic concentrations of norepinephrine and dopamine. These observations suggest that the arousal-enhancing actions of amphetamine-like stimulants involve actions of norepinephrine and/or dopamine. Work in our laboratory is testing this hypothesis. For example, we have identified brain regions within which amphetamine acts to increase arousal, which are identical to those within which norepinephrine acts to increase arousal. Additionally, we are beginning to examine the contribution of norepinephrine and dopamine to amphetamine-induced arousal and identify the receptor subtypes involved in these actions.
Related Publications: Berridge, C.W., O'Neill, J., Wifler, K. (1999) Amphetamine acts within the basal forebrain to initiate and maintain alert waking. Neuroscience 93, 885-896. Berridge, CW and Morris, M. (2000) Amphetamine-induced activation of forebrain EEG is prevented by noradrenergic beta-receptor blockade in the halothane-anesthetized rat. Psychopharmacology, 148:307-313. 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 A.F.T., Castalleno, X. eds. pps. 158-184. back to list of Current Research projects

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