IN-VIVO STUDIES ON THE EFFECTS OF MEMANTINE ON DOPAMINE METABOLISM INTHE STRIATUM AND N-ACCUMBENS OF THE RAT

The action of the amantadine derivative memantine on the dopamine meta bolism in the striatum and the n. accumbens of the rat was studied in vivo with different voltammetrical techniques. It was shown by differe ntial pulse voltammetry that memantine enhanced extracellular levels o f dopamine (DA) in the striatum of the anaesthetized rat, whereas an i ncrease of 3,4 dihydroxyphenylacetic acid (DOPAC) could be observed on ly 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 o nly slightly different from control. These findings suggest that in ad dition to its NMDA receptor antagonism, memantine affects dopaminergic transmission also by other mechanisms.