Effets antiaddictifs de l’extrait hydro-méthanolique des fruits de Citrus medica L.(Rutaceae) sur un modèle d’addiction induit à l’éthanol chez le rat wistar

Abstract

Alcoholism refers to addiction and dependence on alcohol. Harmful alcohol use causes 3 million deaths worldwide each year, accounting for 5.3% of all deaths. Treatment of this pathology is generally based on anxiolytic drugs. However, these palliative treatments are responsible for significant side-effects. Traditional medicine offers an alternative for finding effective drugs with limited side effects. Citrus medica is a small tree in the Rutaceae family, whose fruit is called lemon. It is used in traditional medicine for skin care, to combat addiction and anxiety, and as an antiseptic. The aim of this study was to evaluate the effects of the hydro- methanolic extract of Citrus medica fruit on a rat model of ethanol-induced addiction. 57 rats were divided into two groups as follows: a normal control group (7 rats) received i.p. hydrosaline solution (0.9% NaCl, 10 mL/kg) and an alcohol group (50 rats) received i.p. 10 mL/kg ethanol 20° (V/V). Each animal received daily treatment for 21 days. Twenty-four hours after alcoholization, 35 addicted survivors from the alcohol group were divided into 5 groups of 7 rats each and treated for 18 days as follows: a negative control group received distilled water (10 mL/kg, p.o.); a positive control received diazepam (3 mg/kg p.o.) and three groups treated with the extract at doses of 112, 223 and 446 mg/kg, p.o. To the 5 above-mentioned groups was added the normal control (7 rats) treated with distilled water (10 mL/kg, p.o.). From the sixteenth day of treatment, all rats were subjected to elevated cross maze and open arena tests until the eighteenth day. Twenty-four hours after the behavioral tests, the rats were sacrificed to quantify some neurochemical (GABA, serotonin and dopamine) and oxidative stress (GSH, MDA and SOD) markers in the prefrontal cortex and hippocampus. Histological sections of the prefrontal cortex and hippocampus were then taken. The results reveal that ethanol induced addiction characterized by the onset of anxiety, a decrease (p < 0.001) in the concentration of GABA, serotonin and dopamine in the prefrontal cortex and hippocampus. Ethanol induced oxidative stress characterized by an increase (p < 0.001) in MDA coupled with a decrease in GSH. Ethanol also induced neuronal loss. The extract, on the other hand, increased (p < 0.001) the number of entries and time spent in the open arms of the elevated cross maze. In the open arena, extract increased (p < 0.001) the number of lines crossed, as well as the number of entries and time spent in the central square. Neurochemical analysis indicates that the extract increased (p < 0.001) the concentration of GABA, serotonin and dopamine. The extract decreased (p < 0.001) the concentration of MDA and increased (p < 0.001) that of GSH. Finally, the extract decreased (p < 0.001) the loss of neurons in the prefrontal cortex and hippocampus. These results suggest that the hydro-methanolic extract of Citrus medica fruit has anti-addictive effects mediated by neuromodulatory, antioxidant and neuroprotective activities.