Sitagliptin and Liraglutide Modulate L-dopa Effect and Attenuate Dyskinetic Movements in Rotenone-Lesioned Rats

L-dopa is still considered as the gold standard therapy for Parkinson’s disease (PD); however, L-dopa-induced dyskinesia (LID) is a serious complication of long-term L-dopa treatment. The present study investigated the therapeutic potential of sitagliptin and liraglutide in comparisons with L-dopa against PD. In addition, their capacity to modulate L-dopa dose and/or side effects was investigated, too. Rats were injected with rotenone (3 mg/kg/day, s.c.) for 10 consecutive days to induce the experimental PD. The rotenone-treated rats were administered sitagliptin (30 mg/kg/day, p.o.) and liraglutide (50 μg/kg, s.c.) for 16 days either alone or together with L-dopa/carbidopa (50/25 mg/kg/day, i.p.). Scoring of LID was done on days 2, 4, 8, 12, and 16 in all L-dopa-treated groups. Twenty-four hours after the last administered dose of tested drugs, the behavior of rats in each group was screened by using the open-field test. Sitagliptin and liraglutide revealed marked attenuation of LID scores; in addition, they markedly increased animals’ motor performance. Moreover, they preserved substantia nigra pars compacta (SNpc) tyrosine hydroxylase (TH) and vesicular monoamine transporter 2–positive (VMAT2) cells with prominent increase of the striatal dopamine (DA) content. On the other hand, they significantly decreased nigral neuromelanin (NM)–positive cells, activated microglia, gliosis, and other pathological changes. In conclusion, sitagliptin and liraglutide could be a promising therapeutic challenger in PD, modifying L-dopa effect and/or allowing the use of L-dopa with fewer side effects.