Bradykinesia Induced by Dopamine D2 Receptor Blockade Is Associated with Reduced Motor Cortex Activity in the Rat

Abstract

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 D 2 dopamine receptor antagonist haloperidol. Withincell 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, ϩ231%), 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.

The Effect of Placebo-Induced Changes in Expectancies on Maximal Force Production in College Students

“…For example, in studies with Parkinson's patients, placebo effects have been shown to be partially mediated by dopamine release in the striatum contributing to changes in motor function and performance (e.g., Goetz, Leurgans, Ramman, & Stebbins, 2000) with the degree of dopamine release related to the expectation of clinical benefit (de la Fuente-Fernandez et al, 2001). Changes in dopaminergic function also mediate motor cortex activity, which may alter motor unit recruitment in the spinal cord (e.g., Parr-Brownlie & Hyland, 2005), while recent PET studies demonstrate that placebos activate the limbic system (de la Fuente-Fernandez et al, 2002). One possible explanation, therefore, is that expectancy-induced changes in neural drive produced improved motor unit recruitment and force production.…”

Phosphodiesterase 10A inhibitor, MP-10 (PF-2545920), produces greater induction of c-Fos in dopamine D2 neurons than in D1 neurons in the neostriatum

“…However, these drugs also induce extrapyramidal motor side effects by reducing basal ganglia output (Parr-Brownlie and Hyland, 2005). Although the newer, so-called atypical antipsychotics have a reduced liability to trigger extrapyramidal side effects, they induce intolerable metabolic side effects (Manu et al, 2012).…”

Progressive Motor Cortex Functional Reorganization Following 6-Hydroxydopamine Lesioning in Rats

“…Several studies have attempted to investigate the relationship between motor cortex activity and PD progression, although results have been controversial. Cortical activity has been found to be reduced (Escola et al, 2002(Escola et al, , 2003Buhmann et al, 2003;Lefaucheur, 2005;Parr-Brownlie and Hyland, 2005;Brown et al, 2009), increased (Sabatini et al, 2000;Pelled et al, 2002;Seiss andPraamstra, 2004, Lefaucheur, 2005), or unchanged (Dick et al, 1984;Metz et al, 2004) in parkinsonian animals as well as PD patients. This variability can be attributed to experimental reasons (i.e., methods, time, and region of interest).…”