These experiments characterized motor activity and the extracellular concentrations of dopamine (DA) in the dorsal and ventral striatum with on-line in vivo microdialysis. The first experiment characterized the relationship between dialysate DA and spontaneous motor activity over the day and night in naive rats. The dialysate concentrations of DA in the dorsal striatum increased significantly at night. In contrast, dialysate DA in the ventral striatum did not change across the day and night. Although there was a significant positive correlation between the dialysate DA in both the dorsal and ventral striatum and spontaneous nocturnal motor activity, the relationship was weak, suggesting that regulation of spontaneous motor activity per se is not a primary function of the mesostriatal DA system. Experiments 2 and 3 characterized the changes in spontaneous or AMPH-stimulated motor activity and dialysate DA that occur over time during withdrawal from escalating doses of AMPH. Animals pretreated with AMPH showed a significant decrease in nocturnal motor activity early (3-7 days) during withdrawal, and this was associated with a significant decrease in dialysate DA in the dorsal striatum. In contrast, there was no effect of AMPH withdrawal on dialysate DA in the ventral striatum. These results suggest that the extracellular concentration of DA in the dorsal, but not ventral, striatum may play a role in the behavioral hypoactivity seen early during AMPH withdrawal. Conversely, there was no effect of AMPH pretreatment on spontaneous motor activity or dialysate DA in the dorsal or ventral striatum late (28 days) after AMPH withdrawal. However, the dialysate concentrations of the DA metabolites was significantly enhanced in both regions at this time. In addition, a challenge injection of AMPH produced enhanced motor activity and AMPH-stimulated DA release in both regions, relative to saline-pretreated controls, late, but not early, after AMPH withdrawal. These results suggest that sensitization develops over time after discontinuation of AMPH pretreatment and that enhanced DA neurotransmission may contribute to the behavioral hyperresponsiveness to an AMPH challenge.
Ph.D.
Psychology
University of Michigan, Horace H. Rackham School of Graduate Studies
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