Suppression of alcohol drinking with brain aldehyde dehydrogenase inhibition.

Calcium cyanamide, an aldehyde dehydrogenase (ALDH) inhibitor used in the treatment of alcoholism, strongly suppressed voluntary ethanol drinking by rats. Such inhibitors have generally been believed to act primarily by limiting drinking through acetaldehyde accumulation after ethanol consumption. Administration of a low dose of 4-methylpyrazole (4-MP) that abolished acetaldehyde accumulation did not, however, remove the suppression produced by cyanamide. 4-MP alone did not affect the unsuppressed alcohol intake by Long Evans rats or the drinking by rats of the ANA strain developed for low levels of ethanol consumption. When given from the start with cyanamide, 4-MP did affect the development of the suppression, but probably by its effect in lessening the degree of brain ALDH inhibition: a high correlation (r = +0.825, p less than 0.001) was found between brain ALDH activity and ethanol consumption. The results suggest that cyanamide suppresses alcohol drinking also in the absence of acetaldehyde accumulation probably by some action related to its direct inhibition of brain ALDH.