Neural mechanism of basal gangIia circuit in drug addiction

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To analyze neural mechanism of basal ganglia circuit in drug addiction, we developed a reversible neurotransmission blocking technique, in which transmission of the direct and indirect pathways was selectively and reversibly blocked. The results indicated that the coordinated modulation of these two pathways was necessary for acute psychostimulant actions. This modulation, however, shifted to the predominant roles of the direct pathway in the development of drug addiction by repeated exposure of psychostimulants and rewarding learning and the indirect pathway in aversive learning. Furthermore, we have revealed pathway-specific molecular changes in the substantia nigra pars reticulata after cocaine treatment.