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 alcohol. The purpose of this study was to assess the effect of acamprosate on the function of native NMDA receptors expressed in primary cultured striatal and cerebellar granule cells, as well as ethanol inhibition and spermine modulation of these receptors, using whole-cell patch-clamp electrophysiological techniques. Under all circumstances, acamprosate (0.1-300 microM) did not alter NMDA- or glutamate-induced currents. Acamprosate did not alter the inhibitory effects of ethanol (10-100 mM) on receptor function. In a subpopulation of striatal neurons, acamprosate did reverse the potentiating effects of spermine. These findings indicate that although acamprosate may modify polyamine modulation of the NMDA receptor, acamprosate alone does not alter receptor function nor does it modify ethanol inhibition of this receptor expressed in primary cultured striatal and cerebellar granule neurons.
Popp
R L
RL
Department of Molecular Physiology and Biophysics, Vanderbilt School of Medicine, Nashville, TN 37232, USA. lisa.popp@mail.utexas.edu
Lovinger
D M
DM
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013096:Spermine / Q000494:pharmacology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection
D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D013654:Taurine; D013096:Spermine; D000431:Ethanol; D016202:N-Methylaspartate; D000077443:Acamprosate