Intrastriatal dopamine D1 receptor agonist-mediated motor behavior is reduced by local neurokinin 1 receptor antagonism.

Recent evidence suggests that striatal neurokinin receptors modulate dopamine (DA)-induced motor behaviors. To further examine this, we studied the effects of intrastriatal neurokinin 1 receptor (NK1R) antagonism on motor behaviors induced by direct infusion of the full DA D1 receptor agonist SKF 82958. Adult male Sprague-Dawley rats received bilateral intrastriatal 0.8-mul infusions of the NK1R receptor antagonist LY 306,740 (0, 27, or 54 nmol/side) followed by intrastriatal infusions of SKF 82958 (0 or 24 nmol/side) into the dorsal striatum. Following each infusion, rats were placed into automated activity monitors for the quantification of horizontal activity, total distance traveled, movement bouts, and stereotypy counts. As expected, SKF 82958 increased motor activity on all behavioral measures. More importantly, whereas 27 nmol was without effect, prior infusion of 54 nmol LY 306,740 significantly reduced most aspects of behavior. The results of this study suggest that functional NK1Rs within the striatum play a permissive role in the motor behaviors induced by D1R stimulation.