Reduction of Ethanol-Derived Acetaldehyde Induced Motivational Properties by l-Cysteine

Background: Experimental evidences suggest that acetaldehyde (ACD) contributes to the positive motivational properties of ethanol (EtOH) 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. Cysteine is able to covalently bind ACD thereby forming a stable, nontoxic 2‐methyl‐thiazolidine‐4‐carboxylic acid compound. Thus, we treated rats with l‐cysteine before intragastric administration of EtOH or ACD. Methods: Male Wistar rats were pretreated 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.). Results: 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. Conclusion: 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.