Interaction of acamprosate with ethanol and spermine on NMDA receptors in primary cultured neurons

The N-methyl-D-aspartate (NMDA) receptor has been implicated as a putative sight of action for acamprosate, a novel drug that reduces craving for alco hol. The purpose of this study was to assess the effect of acamprosate on t he function of native NMDA receptors expressed in primary cultured striatal and cerebellar granule cells, as well as ethanol inhibition and spermine m odulation of these receptors, using whole-cell patch-clamp electrophysiolog ical techniques. Under all circumstances, acamprosate (0.1-300 mu M) did no t alter NMDA- or glutamate-induced currents. Acamprosate did not alter the inhibitory effects of ethanol (10-100 mM) on receptor function. In a subpop ulation of striatal neurons, acamprosate did reverse the potentiating effec ts of spermine. These findings indicate that although acamprosate may modif y polyamine modulation of the NMDA receptor, acamprosate alone does not alt er receptor function nor does it modify ethanol inhibition of this receptor expressed in primary cultured striatal and cerebellar granule neurons. (C) 2000 Elsevier Science B.V. All rights reserved.