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

Background: Experimental evidences suggest that acetaldehyde (ACD) contributes to the posi-tive 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 cyste-ine, are known to be effective ACD-sequestering agents. Cysteine is able to covalently bind ACDthereby forming a stable, nontoxic 2-methyl-thiazolidine-4-carboxylic acid compound. Thus, wetreated 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 pref-erence (cpp) (2.5 mg⁄kg, i.p.).Results: l-cysteine dose-dependently prevented both EtOH and ACD-induced cpp but did notinterfere with morphine-induced cpp, suggesting that l-cysteine specifically modulates the motiva-tional 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 ofits rewarding properties and reduce its abuse liability.Key Words: Ethanol, Acetaldehyde, Conditioned Place Preference, l-cysteine, Rat, AlcoholDependence.