A continuing goal of this research project is to identify the neuronal mechanisms underlying the behavioral effects of amphetamine, a widely abused psychomotor stimulant. Attention will center on the striatum, a forebrain region with both cortical and subcortical connections, that processes sensorimotor and motivational information for behavioral output. Proposed experiments involve relating amphetamine-induced changes in the activity of single neurons in the striatum of awake, behaving rats to changes in the focused or nonfocused pattern of the accompanying behavioral response. Individual striatal neurons will be identified in terms of their input-output connections by antidromic activation and by relative location within the patch-matrix organization of the striatum. The actions of amphetamine on intrinsic striatal mechanisms and on corticostriatal afferents will be assessed in a series of studies involving cerebrocortical lesions and intrastriatal amphetamine infusions. Parallel electrophysiological experiments will use a lever-release version of a conditioned avoidance response task to assess striatal mechanisms underlying the performance-enhancing effects of amphetamine-like stimulants, which have been implicated in the high abuse potential of these drugs. Collectively, these lines of investigation will provide important information on the neuronal substrates of stimulant- induced behavioral effects.
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