MODULATORY EFFECT OF AGENTS ACTIVE IN THE PRESYNAPTIC DOPAMINERGIC SYSTEM ON THE STRIATAL DOPAMINE TRANSPORTER

We have investigated the effects of agents active in the presynaptic d opaminergic system on the characterization of the rat striatal dopamin e transporter. The dopamine transporter was characterized by high-affi nity [H-3]GBR 12935 enylmethoxy)-ethyl]-4-(3-phenylpropyl)-piperazine) binding to a membrane preparation and by [H-3]dopamine uptake into st riatal synaptosomes. Subchronic treatment with reserpine (2.5 mg/kg, 4 days), a monoamine depletor, caused a significant decrease in both [H -3]GBR 12935 binding (20%) and [H-3]dopamine uptake (51%). In contrast , amantadine (a dopamine releaser) treatment (20 mg/kg, 21 days) induc ed an increase (28%) in the maximal number of [H-3]GBR 12935 sites. Ch ronic levo-dopa (dopamine precursor) treatment combined with carbidopa (50 mg/kg and 5 mg/kg respectively, 21 days) as well as benztropine ( dopamine uptake inhibitor) treatment (10 mg/kg, 21 days) did not affec t the striatal dopamine transporter characteristics. The present resul ts showed that the striatal dopamine transporter is sensitive to chang es in dopaminergic neurotransmission caused by agents that do not inte ract directly with the dopamine carrier.