This proposal will characterize a portion of the neural circuitry responsible for translating motivationally relevant stimuli into adaptive motor responses. This circuit is termed the motive circuit and contains interconnected brain nuclei which interface between traditional limbic and motor nuclei, including the, nucleus accumbens, ventral tegmental area, ventral pallidum, mediodorsal thalamus and prefrontal cortex. The flow of information through this circuit will be characterized in the context of two behavioral measures, locomotor hyperactivity and spatial delayed alternation in a T-maze. Four neurotransmitter systems will be evaluated, including dopamine, glutamate, GABA and enkephalin using microinjection of transmitter analogues, microdialysis and double labeling techniques to chemically code the anatomical interconnections. In addition, recent studies reveal neuroadaptations within the functional organization of the motive circuit subsequent to dopamine depletion in the nucleus accumbens, and studies are proposed to investigate the basis of this neuroplasticity. Pathophysiological alterations within the motive circuit have been implicated in the etiology and expression of neuropsychiatric disorders, notably in schizophrenia. The information generated by this proposal will identify new opportunities for the pharmacological manipulation of the motive circuit and will provide neurochemical and functional maps that will be useful in evaluating anatomical selectivity in the actions of psychotherapeutic agents. Also, the functional maps generated by this research will have utility in discerning and correlating patterns of change revealed in future brain imaging studies of psychiatric patients and their responses to environmental or pharmacological challenges.
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