Behavioural pharmacologyThe dopaminergic stabilizer pridopidine decreases expression of l-DOPA-induced locomotor sensitisation in the rat unilateral 6-OHDA model

Treatment-limiting motor complications occur in patients with Parkinson's disease after chronic levodopa (l-DOPA) treatment, and represent an unmet medical need. We examined the motor and neurochemical effects of the dopaminergic stabilizer pridopidine (NeuroSearch A/S, Ballerup, Denmark) in the unilateral rodent 6-OHDA lesion model, which is often used to evaluate the potential of experimental compounds for such dopamine-related motor complications. In total, 72 rats were hemi-lesioned and allocated to receive twice-daily injections of either vehicle; 6.5 mg/kg l-DOPA; l-DOPA+25 μmol/kg pridopidine; or l-DOPA+25 μmol/kg (−)-OSU6162-a prototype dopaminergic stabilizer used previously in 6-OHDA hemi-lesion models. Animals were treated for 7, 14 or 21 days, and locomotor activity and ex vivo brain tissue neurochemistry analysed. In agreement with previous studies, l-DOPA sensitised the motor response, producing significantly more contralateral rotations than vehicle (P<0.05). Concomitant administration of pridopidine and l-DOPA significantly decreased the number of l-DOPA-induced contralateral rotations on day 7, 14 and 21 (P<0.05 versus l-DOPA alone), while still allowing a beneficial locomotor stimulant effect of l-DOPA. Concomitant pridopidine also reduced l-DOPA-induced rotation asymmetry (P<0.05 versus l-DOPA alone) and had no adverse effects on distance travelled. Brain neurochemistry was generally unaffected in all treatments groups. In conclusion, pridopidine shows potential for reducing motor complications of l-DOPA in Parkinson's disease and further testing is warranted.