Iino_1993_Neurochem.Int_23_399

Effects of (+/-)-methyl 3-ethyl-2,3,3a,4-tetrahydro-1H-indolo [3,2,1,-de] [1,5] naphthyridine-6-carboxylate hydrochloride (vinconate), an indolonaphthyridine derivative, on the metabolism and function of cerebral cholinergic neurons were investigated using male Wistar rats. Single administration of vinconate (5, 50 and 200 mg/kg) decreased acetylcholine content in the striatum but not those in the cerebral cortex and hippocampus. The same treatment with vinconate (5, 50 and 200 mg/kg, p.o.) had no effect on the activities of choline acetyltransferase and acetylcholinesterase in these brain areas. Although the addition of vinconate (10(-7) - 10(-4) M) had no effect on the high affinity uptake of [3H]choline into striatal slices, it induced a concentration-dependent increase of a KCl(2 x 10(-2) M)-evoked endogenous acetylcholine release. The addition of (-)-sulpiride (10(-8) - 10(-6) M), a dopamine D2 receptor antagonist, also accentuated the KCl(2 x 10(-2) M)-evoked endogenous acetylcholine release form striatal slices. Furthermore, it was found that this (-)-sulpiride (10(-7) M)-induced increase of endogenous acetylcholine release was further augmented by the addition of vinconate (10(-5) M). These results suggest that vinconate may enhance the release of endogenous acetylcholine via the modulation of presynaptic dopamine heteroreceptor in the striatum.