A057: Effects of Aerobic Exercise on Glutamate Homeostasis in NAC DuringWithdrawal Period of Nicotine Addiction

Background/Purpose: The disturbed glutamate homeostasis in the nucleus accumbens (NAc) plays a key role in the induction of relapse during nicotine withdrawal. The uptake of excessive extracellular glutamate relies on astrocytic glutamate transporter-1 (GLT-1) and transporter for cysteine (x-CT). Nicotine abuse leads to decreases in expressions of GLT-1 and xCT in NAc. The purpose of this study was to explore the effects of exercise on the expressions of GLT-1 and x-CT during nicotine withdrawal. Method: (1) 2-month-old male C57BL/6J mice were used in this experiment. Mice were randomly divided into four groups: saline sedentary (SS) group, saline exercise (SE) group, nicotine sedentary (NS) group, and nicotine exercise (NE) group. After the establishment of nicotine addiction model with conditioned place preference (CPP) behavioral paradigm, SE and NE group mice were subjected to moderate intensity treadmill exercise. SS and NS group mice were not given exercise intervention. (2) Exercise program: the first 10min running speed is 12m/min, the last 50min is 15m/min, the slope is 0,60 min/day, 5 days/week, 2 weeks. (3) The nicotine dependence during withdrawal was tested using CPP. (4) The expression of GLT-1 and x-CT in NAc were detected by western blot. (5) The results were expressed as mean ± standard error. Two-way analysis of variance was performed. P &lt; 0.05 was statistically significant. Results: (1) After the establishment of nicotine addiction, CPP scores of NS and NE groups were higher than those in SS group (<italic>P</italic> &lt; 0.001). After two weeks of aerobic exercise, CPP score of NE group was lower than that in NS group (<italic>P</italic> &lt; 0.05). (2) GLT-1 expression in NS group was lower compared with SS group (P &lt; 0.05). GLT-1 expression in NE group was higher compared with NS group (<italic>P</italic> &lt; 0.05). (3) x-CT expression in NS group was lower compared with SS group (<italic>P</italic> &lt; 0.05). x-CT expression in NE group was higher compared with NS group (<italic>P</italic> &lt; 0.01). Conclusion/Discussion: The expressions of GLT-1 and x-CT in the NAc are lower, which might be one of the mechanisms of nicotine relapse during withdrawal. Aerobic exercise increases the expression of GLT-1 and x-CT in the NAc from nicotine withdrawal mice, which might be one of the mechanisms of exercise-induced reduction of nicotine relapse during withdrawal.