Continuous versus pulsatile administration of rotigotine in 6-OHDA-lesioned rats: contralateral rotations and abnormal involuntary movements

Abstract

Sustained drug delivery providing continuous dopaminergic stimulation is thought to prevent or delay the induction of motor complications (dyskinesia) in Parkinson's disease, whereas pulsatile administration is supposed to promote them. This study investigated the inducibility of sensitization and abnormal involuntary movements (AIMs), comparing continuous and pulsatile administration of rotigotine with pulsatile administration of 3,4-dihydroxy-L-phenylalanine (L-DOPA) for reference. Rats were unilaterally lesioned with 6 hydroxydopamine (6-OHDA). For pulsatile administration, L-DOPA-methylester (10 mg/kg L-DOPA i.p.) or rotigotine (1 mg/kg i.p.) were administered once or twice daily. For continuous administration, a slow release formulation of rotigotine was injected s.c. at a dose of 1 mg/kg every 48 h (experiment I) or every 24 h (experiment II). Pulsatile administration of rotigotine and L-DOPA caused contraversive rotations increasing progressively upon each successive treatment. AIMs started to occur after the second administration of L-DOPA but hardly after pulsatile rotigotine. Continuous rotigotine increased rotations, which reached a plateau after the second administration. No AIMs were observed under continuous administration. The continuous administration of rotigotine did not induce sensitization or AIMs, suggesting that continuous stimulation of dopaminergic receptors by rotigotine has no propensity to induce dyskinesia in this experimental model.