Resumo

Objectives: Dopamine-replacement therapy has dominated the treatment of Parkinson’s disease (PD) since the early 1960s. However, a major limitation of chronic dopaminergic therapy is the numerous adverse effects such as the development of abnormal involuntary movements (namely dyskinesia) and On-Off fluctuations. The main objective of this study was to investigate the effects of intranasal (i.n.) administration of L-DOPA on motor performance of reserpinized rats, an experimental model of PD. Methods: A total of 138 adult male Wistar rats were used. The motor performance of independent group of animals treated by intraperitoneal (i.p.) route with reserpine (5 mg/kg) or its vehicle (NaCl 0,9%) was tested 24 h later in the open field (5 min) and the activity chamber (30 min). Thirty min before the motor evaluation, the animals were divided in additional subgroups and received control or L-DOPA (3 or 30 mg/kg) by i.p. or i.n. route. The results were expressed by mean ± standard error. Results and discussion: None of the behavioral parameters (number of crossings and rearings) evaluated in the open field were significantly altered by drug treatments. In the activity cage test, the administration of reserpine induced significant impairments in the locomotor activity of rats as indicated by the decrease in the number of crossings when compared to control group (cont:199,4±9,5; res:68,7±15,0). The appearance of motor impairments in the activity cage seems to be due to a longer evaluation of the animals in comparison to open field. The acute treatment with L-DOPA (regardless the route of administration) did not reverse these motor deficits induced by reserpine. Interestingly, the two tested doses of L-DOPA administered intraperitoneally reduced per se the number of crossings in the activity cage (cont:199,4±9,5; L-DOPA3:149,8±14,1; L-DOPA30:117,71±7,09). However, only the low dose of L-DOPA tested (3 mg/kg) reduced the locomotor activity of rats when administered by i.n. route (cont:148,1±11,9; L-DOPA3:84,6±5,3; L-DOPA30:117,6±9,8). Conclusion: Although the acute treatment with L-DOPA failed to reverse the motor deficits induced be reserpine, the present findings reinforce and extend the notion of the viability of L-DOPA administration by i.n. route. Additional experiments are in progress in our laboratory to evaluate whether the i.n. route can counteract the adverse effects (e.g., dyskinesia) associated to chronic treatment with L-DOPA in rats. Financial support: CNPq, CAPES CEUA/UFSC: PP111