Reinforcing effects of intragastric ethanol-derived acetaldehyde: a conditioned place preference study in the rat

Acetaldehyde (ACD), the first metabolite of ethanol (ETOH), is produced peripherally by gastric and hepatic alcohol dehydrogenase (ADH) and centrally by brain catalase. In spite of the aversive properties classically ascribed to ACD, it has recently been suggested that ACD mediates some of the pleasurable and motivational effects of ETOH (1). Accordingly, the relative role of ACD in the positive motivational properties of ETOH is increasingly becoming matter of debate. Thus, we studied the ability of intragastrically administered ETOH, ACD and ETOH-derived ACD to induce conditioned place preference (cpp) in male Wistar rats. Data showed that both, ETOH at 1 g/kg and ACD at 20 mg/kg were able to induce cpp. Further, in order to investigate the relationship between ETOH and ETOH-derived ACD and to assess if ETOH-derived ACD is involved in the rewarding/reinforcing effects of its parent compound, we used 4- methylpyrazole (4-MP), a competitive inhibitor of ADH (2) and D-penicillamine (DP), an ACD-sequestrating agent (3). Pre-treatment with 4-MP and DP, administered by intraperitoneal injection, both ineffective per se, fully abolished ETOH-induced cpp. Moreover, DP, but not 4-MP, reduced ACD-induced cpp. Furthermore, pre-treatment with 4-MP and DP did not interfere with morphine effect on cpp in rat. Therefore, these findings demonstrated that intragastric ETOH, ACD and ETOH-derived ACD exert similar motivational properties suggesting that ACD plays a key role in the affective/motivational properties of ETOH as well as in its abuse liability. 1) Quertemont et Al., TIPS 25(3): 130-4, 2004 2) Foddai et Al., Neuropsych. 29(3): 530-6, 2004 3) Font et Al., Neuropsych. 184(1): 56-64, 2005