BIPHASIC EFFECTS OF CARBAMAZEPINE ON THE DOPAMINERGIC SYSTEM IN RAT STRIATUM AND HIPPOCAMPUS

To clarify the effects of carbamazepine (CBZ) on dopamine (DA) release and their metabolism, the extracellular and total levels of DA, its m etabolites (DOPAC and HVA) and precursor, 3,4-dihydroxyphenylalanine ( DOPA) in the striatum and hippocampus were studied. DA re-uptake and D OPA accumulation in the striatum and hippocampus, and monoamine oxidas e (MAO) activities were also determined. After acute and chronic admin istrations of CBZ, the plasma concentration of CBZ associated with the rapeutic activity increased the extracellular and total levels of all substances determined, whereas supratherapeutic concentration of CBZ d ecreased extracellular and total levels of all substances. Neither the rapeutic nor supratherapeutic concentrations of CBZ affected MAO-A nor -B activities, nor DA re-uptake. DOPA accumulation caused by NSD1015 was inhibited by therapeutic and supratherapeutic concentrations of CB Z. These results suggest that a therapeutic concentration of CBZ enhan ces DA turnover, whereas a supratherapeutic concentration of CBZ inhib its DA turnover. These effects of CBZ on dopaminergic systems may be, at least partially, involved in the mechanisms of action of CBZ. (C) 1 997 Elsevier Science B.V.