Reduction of ethanol-derived acetaldehyde induced motivational properties by L-cysteine

Acetaldehyde (ACD), the first metabolite of ethanol (EtOH), is produced peripherally by alcohol dehydrogenase (ADH) and centrally by catalase. We have recently suggested that ACD contributes to the positive motivational properties of EtOH ingested, as assessed by the place conditioning paradigm; indeed, we found that by reducing ACD production and/or by using ACD- sequestrating agents, EtOH is deprived from its motivational properties. Thiol products, such as the amino acid cysteine, are known to be effective ACD- sequestering agents. Indeed, cysteine is able to covalently bind ACD forming a stable, non toxic 2-methyl-thiazolidine-4-carboxylic acid compound. Thus, we treated rats intraperitoneally with saline or L-cysteine (10, 20 or 30 mg/kg), before intragastric administration of saline, EtOH (1 g/kg) or ACD (20 mg/kg). The specificity of L-cysteine effect was addressed using morphine-induced conditioned place preference (cpp) (2.5 mg/kg, i.p.). L-cysteine dose- dependently prevented both EtOH and ACD-induced cpp but did not interfere with morphine-induced cpp, suggesting that L-cysteine specifically modulates the motivational properties of EtOH-derived ACD. The present results further underscore the role of EtOH-derived ACD in EtOH-induced motivational properties. L-cysteine, by binding EtOH-derived ACD, would deprive it of its rewarding properties and reduce its abuse liability. EtOH self-administration experiments are currently in progress to further evaluate the role of L-cysteine as a potential treatment for alcohol abuse.