Strain-dependent recovery of open-field behavior and striatal dopamine deficiency in the mouse MPTP model of Parkinson's disease

The neurotoxin MPTP can damage dopamine systems in the brains of rodents, cats, or monkeys, and is therefore widely used to model degenerative processes that underlie human Parkinson's disease. Here, we investigated the relationships between behavioral and neurochemical effects of systemic MPTP treatment in C57BL/6 and Balb/c mice. Initially, different doses of MPTP were used to determine which of them might be useful to establish severe striatal dopamine depletions. These data showed that four injections of 20mg/kg at two hour intervals were more efficient than 10 or 15 mg/kg per injection. However, this dose was not usable due to its severe lethality in females. In contrast, 4 X 15 mg/kg had a low risk of lethality and led to substantial dopamine depletions, which were more severe in the neostriatum than the ventral striatum, and more severe in C57 than in Balb mice. In the first open field test, which was performed two hours after the last injection, this treatment led to severe behavioral inactivation in all parameters taken (distance and speed of locomotion, peripheral activity, frequency and duration of rearing). This effect was seen in both strains and gender. Thereafter, recovery differed between strains, since Balb mice, which had sustained the smaller lesions, had completely recovered on the subsequent day, whereas similar recovery took longer in C57 mice. On the fourth day, all groups appeared largely normal; however, the measure of rearing behavior still showed a deficit in C57 mice. This deficit on day 4 was correlated with neostriatal dopamine depletion; that is, the larger the lesion, the less the number and duration of rearings. Interestingly, these relationships were also observed with respect to ventral striatal dopamine damage, which was correlated with the rearing deficit not only on day 4, but also on day 1. These data will be discussed with respect to mechanisms of toxicity, functional recovery, and the function of striatal dopamine systems.