Effect of quetiapine on levels of glutamate and expression of cannabinoid receptor 1 in the hippocampus of rats with chronic alcoholism

Abstract

Objective To observe the effect of quetiapine on levels of glutamate and expression of cannabinoid receptor type 1 (CB1) in the hippocampus of rats with chronic alcoholism. Methods Forty-eight rats were randomly divided into 4 groups of 12: control group, chronic alcoholism group, low and high quetiapine groups (both with chronic alcoholism), to establish an animal model of chronic alcoholism. The abstinence scoring was used to evaluate the rats′ withdrawal symptom; the concentrations of glutamate in rats′ hippocampus were measured by high-performance liquid chromatography (HPLC); expression of CB1 mRNA was evaluated by real-time quantitative PCR, CB1 protein expression in the hippocampus was detected by immunofluorescence. Results The abstinence score (11.20 ± 3.01 vs. 5.50 ± 1.90), glutamate content （(0.26 ± 0.06) μmol/g vs.(3.55 ± 0.67) μmol/g）, CB1 mRNA relative copy numbers (7.53 ± 0.80 vs. 1.83 ± 0.81) were significantly different in the chronic alcoholism group as compared to the control group （t=5.06, 15.52, 15.88, all P<0.05). The abstinence score（6.70 ± 1.34 vs.11.20 ± 3.01）, glutamate content（(2.56 ± 0.55) μmol/g vs.(0.26±0.06) μmol/g）, CB1 mRNA relative copy numbers (1.95±0.65 vs.7.53 ± 0.80) were also significantly different in the high quetiapine group as compared to the chronic alcoholism group （t=4.32, 13.19, 17.11, all P<0.05); immunofluorescence showed that CB1 positive cells in the chronic alcoholism group were significantly increased compared with the control group, and CB1 positive cells in the high quetiapine group were significantly decreased compared with the chronic alcoholism group. Conclusion Quetiapine may alleviate the damage from chronic alcoholism, the mechanism may be relate to the regulation of the CB1/glutamate pathway. Key words: Alcoholism; Quetiapine; Glutamic acid; Receptor, cannabinoid, CB1