EFFECTS OF D1 AND D2 AGONISTS ON SPONTANEOUS MOTOR-ACTIVITY IN MPTP TREATED MICE

Two experiments were performed to study the effect of combining bromoc riptine with SKF 38393 (SKF), or vice/versa, upon parameters of sponta neous motor activity in MPTP treated and saline (control) treated mice . Treatment with MPTP (2 x 40 mg/kg, subcutaneously) induced a hypoact ive condition compared with saline treated mice. Bromocriptine (10 mg/ kg, subcutaneously), administered to MPTP mice 2 hr, but not 1 or 4 hr , after SKF (6 mg/kg, subcutaneously) caused a marked increase in loco motion and rearing behaviour. The administration of bromocriptine (10 mg/kg, subcutaneously) 4 hr before SKF (6 mg/kg, subcutaneously) eleva ted all three parameters of spontaneous activity-in the MPTP treated m ice, independent of the injection of SKF Bromocriptine injection 1 or 2 hr before SKF decreased locomotion in both MPTP and control mice. Ne urochemical analysis confirmed the dopamine depletion in the MPTP trea ted mice. These results are discussed in terms of the reliability of t he MPTP model of parkinsonism in mice and the dopamine D1/D2 receptor hypersensitivity following denervation with the neurotoxin.