Distinct effects of amantadine and memantine on dopaminergic transmission in the rat striatum.
Striatal glutamatergic inputs are known to participate in the modulation of dopaminergic transmission. Accordingly, the non-competitive N-methyl-D-aspartate receptor antagonists memantine and amantadine increase striatal dopamine levels, the latter being widely used in Parkinson's disease therapy. Based on our previous work revealing increased function of dopamine receptors and dopamine transporter after amantadine treatment, we studied the effects of repeated memantine administration on dopaminergic neurotransmission. On rat striatal membranes, dopamine-stimulated [(35)S]GTPgammaS binding was significantly reduced (20%) after 2 days injection with memantine (20 mg/kg per day, i.p.) but not after longer treatments (4 or 7 days). Evaluation of [(3)H]SCH 23390 and [(3)H]spiperone specific bindings only revealed a significant increase in D1 receptor density after 4 or 7 days treatment. Finally, none of these treatments were found to change the activity of the neuronal dopamine transporter in striatal synaptosomes. This shows that amantadine and memantine differentially affect striatal dopaminergic transmission, which could indicate that these two related aminoadamantanes display distinct pharmacodynamic properties.
Peeters
Magali
M
Laboratoire de Pharmacologie Expérimentale (FARL), Université Catholique de Louvain 54.10, Avenue Hippocrate 54, B-1200 Brussels, Belgium.
Maloteaux
Jean-Marie
JM
Hermans
Emmanuel
E
D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013134:Spiperone / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D018721:Muscarinic Agonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013134:Spiperone; D002217:Carbachol; D000547:Amantadine; D004298:Dopamine; D008559:Memantine