Bradykinesia induced by dopamine D2 receptor blockade is associated with reduced motor cortex activity in the rat

Disruption of motor cortex activity is hypothesized to play a major role in the slowed movement (bradykinesia) associated with reduced dopaminergic function. We recorded single neurons in the motor cortex of free-moving rats performing a forelimb-reaching task. The same neurons were examined before and after induction of bradykinesia with the D2 dopamine receptor antagonist haloperidol. Within-cell changes in the firing rate and firing pattern of individual cells and the correlation between simultaneously recorded cells after injection of haloperidol were statistically compared with vehicle-only control experiments. During haloperidol-induced bradykinesia (mean movement time increase, +231%), there was an average 11% decrease in baseline firing rate. Movement-related peaks in firing rate were more dramatically affected, with an overall reduction in peak amplitudes of 40%. Bradykinesia was also associated with decreased intensity of bursting and amplitude of cross-correlation peaks at rest. The results show for the first time that significant reductions can be detected in motor cortex activity at rest in animals with impaired ability to generate movements induced by reduced dopamine action and confirm that impaired movements are associated with reduced cortical activation. Together, these changes in neural activity may reduce recruitment and rate modulation of motor units in the spinal cord.