Distinct effects of amantadine and memantine on dopaminergic transmission in the rat striatum
Autor: | Emmanuel Hermans, Jean-Marie Maloteaux, Magali Peeters |
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Rok vydání: | 2003 |
Předmět: |
Male
medicine.medical_specialty Spiperone Dopamine Dopamine Agents In Vitro Techniques Muscarinic Agonists Synaptic Transmission Dopamine receptor D1 Memantine Internal medicine medicine Amantadine Animals Rats Wistar Dopamine transporter Membranes biology General Neuroscience Dopaminergic Benzazepines Rats Neostriatum Kinetics Endocrinology Dopamine receptor Guanosine 5'-O-(3-Thiotriphosphate) biology.protein Dopamine Antagonists Carbachol medicine.drug Synaptosomes |
Zdroj: | Neuroscience letters. 343(3) |
ISSN: | 0304-3940 |
Popis: | 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. |
Databáze: | OpenAIRE |
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