Atrial natriuretic peptide modulates N-methyl-D-aspartate-induced hyperexcitability in ethanol-dependent mice

The role of central nervous atrial natriuretic peptide was investigated for behavioral hyperexcitability in alcohol-dependent mice. Mice were made tolerant to and dependent on ethanol with an ethanol-liquid diet for 14 days. Five hours after withdrawal from ethanol, withdrawal symptoms were analyzed by scoring handling-induced convulsions. N-methyl-D-aspartate (NMDA) induced behavioral seizures in a dose-dependent manner, an effect which was more intensive during the ethanol withdrawal period than in alcohol-naive animals. Intracerebroventricular (i.c.v.) injections of alpha-atrial natriuretic peptide (atrial natriuretic peptide) dose-dependently inhibited, whereas injection of an antiserum against atrial natriuretic peptide potentiated, the seizure-inducing effect of NMDA in ethanol-dependent mice. The main conclusion is that central nervous atrial natriuretic peptide plays a modulatory role in behavioral hyperexcitability during alcohol withdrawal.