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 loco motor patterns were tested in rats at 4 months of age. Measurements we re taken using an activity pattern monitor. The lesioned group was sig nificantly hypoactive in comparison to the control animals during the initial exposures to the monitor. Examination of locomotor paths indic ated that the lesioned animals failed to develop the increasingly orga nized 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 D-1-dopamine agonist, SKF-38393 (3.0 mg/kg) were investigated. A priming effect, leading to increases in am bulations and fine movements, was observed only in the lesioned animal s after repeated administration of SKF-38393. The D-1-dopamine agonist did not change the activity of the unlesioned animals and did not lea d to persistent effects in lesioned animals tested 2 and 4 days follow ing the final drug administration. Across the duration of the second s tudy, the lesioned group did not demonstrate hypoactivity. Overall, th e experiments showed that neonatal dopamine, depletion disrupts the no rmal patterns of behavior associated with habituation to a novel envir onment, and repeated administration of SKF-38393 can further alter the se abnormal activity patterns.