Altered activity patterns following neonatal 6-hydroxydopamine lesions to dopaminergic neurons: effect of SKF-38393

The effects of neonatal dopamine depletion on activity levels and locomotor patterns were tested in rats at 4 months of age. Measurements were taken using an activity pattern monitor. The lesioned group was significantly hypoactive in comparison to the control animals during the initial exposures to the monitor. Examination of locomotor paths indicated that the lesioned animals failed to develop the increasingly organized spatial behavior observed in control animals. In a second study, changes in motility and locomotor patterns before, during, and after the repeated administration of a D1-dopamine agonist, SKF-38393 (3.0 mg/kg) were investigated. A priming effect, leading to increases in ambulations and fine movements, was observed only in the lesioned animals after repeated administration of SKF-38393. The D1-dopamine agonist did not change the activity of the unlesioned animals and did not lead to persistent effects in lesioned animals tested 2 and 4 days following the final drug administration. Across the duration of the second study, the lesioned group did not demonstrate hypoactivity. Overall, the experiments showed that neonatal dopamine depletion disrupts the normal patterns of behavior associated with habituation to a novel environment, and repeated administration of SKF-38393 can further alter these abnormal activity patterns.