Potentiation by deprenil of 1-dopa induced circling in nigral-lesioned rats

Abstract

1-Deprenil, a potent inhibitor of type B monoamine oxidase, was a weak inhibitor of 3H-dopamine uptake as well as a weak releasing agent for previously accumulated 3H-dopamine in rat neostriatal tissue slices. In similar experiments d-amphetamine as approximately 100 times as potent as 1-deprenil as a releasing agent. When deprenil (20 mg/kg IP) was given to rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra, it brought about a moderate but long-lasting ipsilateral rotational behavior. 1-Dopa (20-40 mg/kg, IP) by itself caused a considerably stronger rotation in the opposite direction (contralateral). When 1-dopa was given to rats 1 hr after 1-deprenil, there was a considerably greater contralateral rotation than after 1-dopa alone. Clorgyline, a type A monoamine oxidase inhibitor, which by itself at 20 mg/kg caused no rotation, also potentiated the contralateral rotation seen after 1-dopa (5-20 mg/kg). In contrast, d-amphetamine, which by itself caused ipsilateral rotation, failed to potentiate the rotation after 1-dopa. Possible mechanisms for these observations will be discussed.