Neurobehavioural Changes in a Hemiparkinsonian Rat Model Induced by Rotenone

Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study.

To assess all the motor deficits in lesioned animals that are due to the depletion of dopaminergic neurons or its terminals, the lesioned animals were administered with anti-parkinsonian drug, Levodopa which should counteract motor deficits in rats.

The unilateral partially lesioned PD model was induced by rotenone stereotaxically into two sites of striatum of male Wistar albino rats at a dosage of 25 μg of rotenone/site. Rats were tested for its neurobehavioural activity on 7^th day, 14^th day, 21^st day and on 30^th day after rotenone infusion and compared with the sham group and sacrificed on 21^st and 30^th day for microscopic studies. L-DOPA was administered from 21^st day to 30^th day after lesion and compared with the lesioned group for the motor performance and sacrificed on 30^th day for histology. Statistical analysis using One-way Analysis of variance followed by Tukey's test was applied for behavioural studies.

Statistical analysis showed that the signs and symptoms like motor in-coordination and postural disturbances are highly significant (p<0.05) on 14^th and 21^st day after administration of rotenone when compared to sham group. In L-DOPA treated rats, all the motor deficits were reversed. The neuronal cell death was minimal and sprouting of nerve terminals was detected. In lesioned group, the degeneration of nerve terminals and striatal neurons were in progressive manner.

These findings suggest that intrastriatal infusion of rotenone at a moderate dose could be used for producing hemiparkinsonian partially lesioned animal model without any mortality. Hence, this model is suitable for evaluating behavioural studies and in drug screening programs even for a long term study.