Resumo

OBJECTIVES: Many studies have shown that alterations in olfactory, cognitive and emotional functions precede the classical motor symptoms seen in Parkinson's disease (PD). Mood stabilizers such as lithium (Li) and valproic acid (VPA) are used to treat bipolar mood disorder and more recently they have been suggested as potential neuroprotective agents. The aim of the present study was to evaluate the potential of Li and VPA to prevent the olfactory and cognitive deficits in rats infused with a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an animal model of PD developed by our group. Methods. Adult male Wistar rats were pre-treated with Li (47.5 mg/kg) or VPA (200 mg/kg) by intraperitonial (i.p.) route for 7 days before a single bilateral i.n. infusion of MPTP (1 mg/nostril) and them the animals were evaluated during different intervals (2-14 days) in a battery of behavioral tests that included the olfactory discrimination, social recognition, open-field and forced swimming tasks. RESULTS: Most of the impairments presented by rats infused with MPTP were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and cognitive deficits with no major motor impairments. Of high interest, the present results indicated that the pre-treatment with Li and VPA were able to prevent the olfactory deficits [%time in familiar compartment: Cont:59.7+4.3; MPTP:48.7+3.4; Li+MPTP:60.7+3.7; VPA+MPTP:57.5+4.4] and short-term social recognition memory [ratio of investigation duration: Cont:0.5±0.1; MPTP:0.8±0.1; Li+MPTP:0.6±0.1; VPA+MPTP:0.6±0.1). In the forced swimming test, although MPTP administration did not induce a depressive-like symptom, the treatment with Li and VPA reduced the immobility time [immobility time(s): Cont:9.2±6.2; MPTP:10.8±4.3; Li+MPTP:2.6±0.5; VPA+MPTP:2.8±1.3]. At this time, no significant alterations on the locomotor activity were observed in the open-field. Conclusion: These results provide new insights in experimental models of PD, indicating that the mood stabilizers agents Li and VPA may represent new therapeutic tools for the prevention of olfactory and emotional symptoms associated to early preclinical phases of PD.