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 dopaminergic system on the characterization of the rat striatal dopamine transporter. The dopamine transporter was characterized by high-affinity [3H]GBR 12935 (1-[2-diphenylmethoxy)-ethyl]-4-(3-phenylpropyl)-piperazine) binding to a membrane preparation and by [3H]dopamine uptake into striatal synaptosomes. Subchronic treatment with reserpine (2.5 mg/kg, 4 days), a monoamine depletor, caused a significant decrease in both [3H]GBR 12935 binding (20%) and [3H]dopamine uptake (51%). In contrast, amantadine (a dopamine releaser) treatment (20 mg/kg, 21 days) induced an increase (28%) in the maximal number of [3H]GBR 12935 sites. Chronic 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 affect the striatal dopamine transporter characteristics. The present results showed that the striatal dopamine transporter is sensitive to changes in dopaminergic neurotransmission caused by agents that do not interact directly with the dopamine carrier.
Gordon
I
I
Department of Physiology, Tel Aviv University, Israel.
Weizman
R
R
Rehavi
M
M
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D001590:Benztropine / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D012110:Reserpine / Q000494:pharmacology
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D001590:Benztropine; D007980:Levodopa; D012110:Reserpine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D000547:Amantadine; D004298:Dopamine