Chronic Ethanol Consumption Impairs Mouse Motor Coordination Function Via NO Sygnalling Pathway

Objective:The aim of this study is to study the effects of chronic alcohol intake on motor coordination and to explore the mechanism of the effects of chronic alcohol intake on motor coordination in mice by motor behavioral tests and pharmacological methods.Methods:Fifty ICR male mice(6-8 weeks old)were divided into 5 groups,which included control group,low-dose alcohol group,high-dose alcohol group,high-dose alcohol+L-NNA group and high-dose alcohol +AM251 group(10 mice in each group).The control group was intraperitoneally injected with 9g/kg saline,the low-dose group was injected with 0.8g/kg ethanol,and the high-dose group was injected with 1.6g/kg ethanol.The injection cycle of each group was 28 days.After 28 days intraperitoneal injection of alcohol,the motor coordination function was examined on the first day,the first week,the second week and the third week using the locotronic analyzer and the rotarod.The high-dose alcohol+L-NNA group and the high-dose alcohol+AM251 group were injected with nitric oxide synthase inhibitor(L-NNA;1mg/kg)and cannabinoid receptor 1(CB1)receptor inhibitor(AM251;10mg/kg),respectively.After the injection of L-NNA and AM251,the motor behavior of mice was observed.Data were analyzed using SPSS 17.0 analysis software,then one-way analysis and student's t test was used for comparison of mean values of each group.P<0.05 was considered statistically significant.Results:(1)The number and duration of gait errors of mice in the chronic alcohol intake group were significantly higher than those in the control group(P<0.05).However,the number and duration of gait errors were significantly increased in the high-dose group and in the low-dose group(P<0.05).These results suggested that chronic ethanol consumption impaired motor coordination in a dose-dependent manner.(2)Compared with the control group,the duration and rotation speed of mice in the alcohol intake group were significantly shortened,with statistical significance(P<0.05).(3)Intraperitoneal injection of NO synthase inhibitor(L-NNA)improved the injury effect of alcohol intake on motor coordination,which expressed a significant reduction in the number and duration of gait errors.and significant increase in the duration and rotation speed on the rotarod than alcohol consumption group(P<0.05).(4)After intraperitoneal injection of CB1 receptor inhibitor(AM251),there were no statistically significant differences in the number and time of gait,as well as the duration and rotation speed on the rotors in mice exposed to alcohol compared with those before administration(P>0.05).(5)The impairment effect of ethanol intake on motor coordination function of mice gradually decreased after stopping ethanol intake,and completely subsided after 3 weeks,returning to the level before ethanol intake.Conclusions:(1)Chronic ethanol consumption has a significant effect on the regulation of motor function in mice,which is achieved through the NO signaling pathway,but has nothing to do with the activation of CB1 receptor.(2)The effects of chronic ethanol consumption on motor coordination in mice were reversible and subsided after 3 weeks.