Research aimed at characterizing the behavioral effects of amphetamine and related stimulants, including cocaine, has been useful for identifying their possible mechanisms of action. Both the neostriatum and the nucleus accumbens, which are critically involved in sensorimotor functioning, have been implicated in stimulant-induced behavioral effects. In this application, these brain regions will be studied in freely moving animals in order to obtain temporally and anatomically discrete information on the neuronal events underlying stimulant induced behavioral responses. Attention will center on acute and chronic stimulant-induced changes in neostriatal and nucleus accumbens output neurons during periods of locomotor activation and focused stereotyped responding. Antipsychotic drugs, which block the euphoriant and rewarding effects of amphetamine, will be used to probe the mechanisms underlying stimulant-induced neuronal- behavioral isomorphisms. The neostriatum and nucleus accumbens also will be examined during performance of a conditioned avoidance response task in order to investigate the neural substrates of the performance-enhancing effects of amphetamine. A parallel series of experiments will probe these same brain regions in freely moving animals to monitor stimulant-induced changes in extracellular ascorbate, a compound known to be released by these drugs and to attenuate their behavioral effects.
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