Effects Of Aerobic Exercise On Learning Memory And Monoamine Neurotransmitters In Alcohol Use Disorder Mice

Objective: This study investigated the effects of aerobic exercise on learning and memory in mice with alcohol use disorder(AUD)after abstinence,and revealed the molecular mechanisms for the learning and memory of the moderate-intensity exercise intervention in AUD mice through the levels of monoamine neurotransmitters in the hippocampus.Methods: 7-week-old C57BL/6J male mice were used for the study,and after 12 mice were randomly selected as sentinel mice,the remaining mice were randomly divided into alcohol use disorder(AUD)and control(Con)groups according to body mass in a randomized zone design.After the two-bottle choice(sucrose fading and normal 2-bottle choice)and chronic intermittent ethanol vapor exposur e(alcohol vapor exposure combined with intraperitoneal injection)co-construction of AUD model,the mice were randomly divided into control sedentary(Con-Sed),control exercise(Con-Ex),alcohol use disorder sedentary(AUD-Sed)and alcohol use disorder exercise(AUD-Ex)groups as previously described method,followed by treadmill exercise for the Ex group.After 8 weeks of exercise,the open field test and Morris water maze were performed.ELISA kits were used to detect dopamine(DA),norepinephrine(NE),serotonin(5-HT)and brain-derived neurotrophic factor(BDNF)in the hippocampus.Results:(1)Changes in AUD mice after modeling: drinking was higher after 4 weeks of ethanol vapor exposure than after 1 week of exposure(p<0.05).The blood ethanol concentration of se ntinel mice was maintained in the range of 200-220 mg/dl.No significant differences were seen in the results of the open field test between the groups of mice(p>0.05).In the Morris water maze,compared with the Con,the mice in the AUD group showed a si gnificant increase in escape latency(p<0.001)and a significant decrease in the number of target platform crossings(p<0.05),but no significant differences were seen in the swimming speed(p>0.05).(2)Changes after aerobic exercise intervention: no sign ificant differences were seen in body weights of mice in all groups(p>0.05).No significant differences were seen in the results of the open field test between the groups of mice(p>0.05).In the Morris water maze,the escape latency of mice in the AUD-Sed group was longer than that in the AUD-Ex(p<0.01)and Con-Sed(p<0.05)groups,respectively.T he number of target platform crossing in the AUD-Ex group was more than that in the AUD-Sed group(p<0.05),and no significa nt differences were seen in the swimming speed of each group(p>0.05).The hippocampal weight and BDNF content in the AUD-Ex group were higher than those in the AUD-Sed(p<0.05),and the Con-Ex group was significantly higher than that in the Con-Sed(p<0.05).Compared with the AUD-Sed,DA and NE contents in the hippocampus of both the AUD-Ex and Con-Sed groups were significantly reduced(p<0.01).The DA content was significantly increased in both AUD-Ex and Con-Sed compared to Con-Ex group(p<0.05).5-HT content in hippocampus was lower in AUD-Ex group than in AUD-Sed(p<0.05).Conclusions:(1)In this study,a combination of voluntary ethanol consumption and forced inhalation of ethanol vapor is used to successfully replicate the AUD model in mice.(2)After the modeling of AUD,the degree of spontaneous activity and anxiety state of AUD mice are not significantly different from those of normal mice,but the learning and memory is significantly reduced.(3)After withdrawal from ethanol,the learning and memory of AUD mice has not yet returned to normal levels,while aerobic exercise can improve their learning and memory,which is related to the fact that exercise can improve the disorder of monoamine neurotransmitters in the hippocampus,increase BDNF levels and hippocampal mass.