In vivo studies on the effects of memantine on dopamine metabolism in the striatum and n. accumbens of the rat.
The action of the amantadine derivative memantine on the dopamine metabolism in the striatum and the n. accumbens of the rat was studied in vivo with different voltammetrical techniques. It was shown by differential pulse voltammetry that memantine enhanced extracellular levels of dopamine (DA) in the striatum of the anaesthetized rat, whereas an increase of 3,4 dihydroxyphenylacetic acid (DOPAC) could be observed only under freely moving conditions using square wave voltammetry. Under chloral hydrate anaesthesia the effect of memantine on extracellular DOPAC levels in the striatum and the n. accumbens was compared with MK-801, a well-known non-competitive NMDA-antagonist. Memantine did not affect striatal DOPAC concentrations under these conditions whereas MK-801 reduced the DOPAC signal. In the n. accumbens memantine enhanced the levels of extracellular DOPAC, while after MK-801 the signal was only slightly different from control. These findings suggest that in addition to its NMDA receptor antagonism, memantine affects dopaminergic transmission also by other mechanisms.
Clement
H W
HW
Department of Neurochemistry, Philipps University, Marburg/Lahn, Federal Republic of Germany.
Grote
C
C
Svensson
L
L
Engel
J
J
Zöfel
P
P
Wesemann
W
W
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000978:Antiparkinson Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D016291:Dizocilpine Maleate; D004298:Dopamine; D008559:Memantine