Somatodendritic dopamine release in rat substantia nigra influences motor performance on the accelerating rod

The physiological role of somatodendritic dopamine release in the rat substantia nigra was evaluated with a combination of dual probe microdialysis and simultaneous motor performance tests on an accelerating rod. Three main findings support a modulating influence of somatodendritic dopamine release on motor coordination. (1) The rod performance tests were associated with an increase in extracellular dopamine but not 5-hydroxytryptamine concentrations in substantia nigra and wit h increases in both dopamine and 5-hydroxytryptamine concentrations in the striatum. (2) Nigral application of dopamine antagonists without intrinsic activity resulted in changed performances on the accelerating rod. The response to nigral perfusion with low concentrations (0.1, 1.0 muM) of the D-2/D-3-antagonist raclopride consisted of an impairment in rod performance to 63% of the pre-perfusion performance. Higher concentrations (10, 100 muM), however, were not associated with impaired rod performance, but with increased striatal dopamine concentrations. Perfusion of the substantia nigra with 1, 10 and 100 muM of the D-1/D-5-antagonist SCH 23390 dose-dependently impaired rod performance. SCH 23390 consistently increased dopamine and 5-hydroxytryptamine concentrations in substantia nigra but did not change the dialysate in the striatum. (3) In unilaterally 6-hydroxydopamine-lesioned rats, a dose-dependent improvement in rod performance was observed during perfusion of the substantia nigra with the non-selective dopamine agonist apomorphine. (C) 2003 Elsevier Science B.V. All rights reserved.