Involvement of ventrolateral striatal dopamine in movement initiation and execution: a microdialysis and behavioral investigation.

Abstract

Previous studies have demonstrated that the ventrolateral region of the rat neostriatum is the site at which dopamine depletions produce profound motor deficits that interfere with food handling and lever pressing. In the present work, two experiments were undertaken to investigate the role of ventrolateral striatal dopamine in lever pressing. The first experiment was a detailed characterization of the motor impairments induced by injections of the neurotoxic agent 6-hydroxydopamine into the ventrolateral striatum. Behavioral output during lever pressing on a fixed ratio 5 schedule was recorded by a computerized system that measured the duration and response initiation time for each lever press. Response initiation time was defined as the time from offset of one lever press to the onset of the next one. Dopamine depletions resulting from 6-hydroxydopamine injections profoundly depressed lever pressing response rate. This deficit was largely due to a dramatic increase in the average response initiation time. Analysis of the distribution of response initiation times indicated that dopamine-depleted rats made relatively few responses with fast initiation times (e.g. 0-125 ms), and also that dopamine depletions led to a dramatic increase in the number of pauses in responding (i.e. response initiation times greater than 2.5 s). This slowing of the initiation of movement was very sensitive to the effects of dopamine depletions, and even animals with mild dopamine depletions (29.1% of control levels) showed increased initiation times. Analysis of response durations indicated that dopamine depletions resulted in a shift in the distribution of durations such that depleted rats had a modal response duration of 375-500 ms, in contrast to the control mode of 125-250 ms. There was an overall increase in average response duration among animals with more severe dopamine depletions, although rats with moderate depletions showed no change in average response duration. In the second experiment, in vivo dialysis methods were used to study the dynamic activity of ventrolateral striatal dopamine during lever pressing. During the performance of a 30-min fixed ratio 5 lever pressing session, there was a small but significant increase (20.9% above baseline) in dopamine release. There was not a linear or curvilinear correlation between lever pressing rate and increases in dopamine release. The relatively modest increase in ventrolateral striatal dopamine release during lever pressing and the lack of relation between dopamine release and behavioral output may indicate that dopamine in the ventrolateral striatum plays mainly a permissive role in lever pressing. These results suggest that ventrolateral striatal dopamine depletions in rats produce deficits in skilled motor control that are similar to the motor deficits observed in patients with Parkinson's disease.