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

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.

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.).

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.

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.