Attenuation of preparatory activity for reaching movements by a D1-dopamine antagonist in the monkey premotor cortex

To examine the role of dopamine receptors in the function of the premotor cortex (PM) for preparing for reaching movements, dopamine antagonists (SCH23390 for D1 receptors and sulpiride for D2 receptors) were applied iontophoretically to neurons of the PM of monkeys that performed a delayed-reaching (DR) task with their arms. In the DR task, the monkey made a reaching movement to one of three target levers (left, upper, and right), which had been cued by a visuospatial stimulus before a delay period of 4 s. We focused on neurons (n = 56) that showed a sustained increase in activity during the delay period (delay-period activity; i.e., "set-related" activity), because such activity is considered to play a central role in preparing for forelimb movements. Iontophoretic application of SCH23390 (usually with a current of 50 nA) significantly decreased the activity of most of these neurons (n = 44/56, 79%), and delay-period activity was attenuated during its application. In contrast, application of sulpiride or SCH23388 (an inactive analogue of SCH23390), using the same current intensity, had no effect on most of the neurons tested with these drugs (n = 31/33 and n = 21/23, respectively), despite the fact that their activity was decreased by SCH23390. Furthermore, for neurons that were affected by SCH23390, the percent decrease in delay-period activity was significantly greater than the percent change in background activity. In more than one-half of the neurons (n = 26/44, 59%), background activity was either increased (n = 10) or not affected (n = 16) by SCH23390, even though it significantly attenuated delay-period activity. These findings suggest that the activation of D1-dopamine receptors plays a modulatory role in PM function in preparing for reaching movements.