Experimental models of Parkinson’s disease with levodopa-induced dyskinesias and gait dysfunction: electrophysiological and behavioural measures in rats

Objective: The pathophysiological mechanisms leading to dyskinesias in Parkinson’s disease (PD) after long-term treatment with levodopa remain unclear. This study investigates the neuronal firing characteristics of the entopeduncular nucleus (EPN), the rat equivalent of the human globus pallidus internus and output nucleus of the basal ganglia, and its coherence with the motor cortex (MCx) field potentials in the unilateral 6-OHDA rat model of PD with and without levodopa-induced dyskinesias (LID). Methods: 6-hydroxydopamine lesioned hemiparkinsonian (HP) rats, 6-OHDA lesioned HP rats with LID (HP-LID) rats, and näıve controls were used for recording of single unit activity under urethane (1.4 g/kg, i.p.) anesthesia in the EPN “on” and “off” levodopa. Over the MCx, the electrocorticogram (ECoG) was recorded. Results: Analysis of single unit activity in the EPN showed enhanced firing rates, burst activity and irregularity compared to näıve controls, which did not differ between drugnäıve HP and HP-LID rats. Analysis of EPN spike coherence and phase locked ratio with MCx field potentials showed a shift of low (12-19Hz) and high (19-30Hz) beta oscillatory activity between HP and HP-LID groups. EPN theta phase locked ratio was only enhanced in HP-LID compared to HP rats. Overall, levodopa injection had no stronger effect in HP-LID rats than in HP rats. Conclusions: Altered coherence and changes in the phase lock ratio of spike and local field potentials in the beta range may play a role for the development of LID.