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The aim of the study was to investigate whether acamprosate, an agent attenuating relapse in human alcoholics, might modulate antioxidant status in rats chronically administered ethanol. Male Wistar rats were presented with a free choice paradigm between tap water and ethanol solution for three month to distinguish two groups of animals, preferring (PRF) and non-preferring (NPF) ethanol. Then, rats were administered acamprosate, 500 mg/kg/day, per os, for 21 days. The hepatic level of enzymatically-driven lipid peroxidation was enhanced by ethanol in PRF and NPF rats by 67 and 82%, respectively. Unstimulated microsomal lipid peroxidation was increased solely in NPF rats by 33%. Acamprosate caused 36% increase in stimulated lipid peroxidation only in NPF animals. The activities of all hepatic antioxidant enzymes examined: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase were decreased in rats treated with ethanol by 30 to 64% as compared to controls, however, this decrease was more distinct in ethanol preferring rats. Administration of acamprosate further reduced the activity of antioxidant enzymes only in NPF rats: catalase by 47%, glutathione peroxidase and glutathione S-transferase by 37% and glutathione reductase by 33%. No effect of acamprosate on 4-nitrophenol hydroxylase, a marker of CYP2E1 activity, was observed. As acamprosate enhanced oxidative stress only in the rats non-preferring ethanol, it could be expected that these adverse effects are not demonstrated in alcohol-dependent humans treated with acamprosate.

The effect of 5-week voluntary ethanol (EtOH) intake on plasma and cerebrospinal fluid (CSF) leptin levels was determined in adult male Warsaw high EtOH preferring (WHP) and low preferring (WLP) rats. EtOH treatment led to a decrease in leptin CSF concentration in WHP rats when compared to EtOH-naive WHP and control Wistar rats. On the contrary, in EtOH-treated WLP rats, both plasma and CSF leptin levels were increased in comparison with EtOH-naive animals. It can be concluded that EtOH treatment led to different response expressed especially by CSF leptin levels in WHP and WLP animals and it may be related to their genetic predisposition.