Hui Huang1,2, Xiaojie Zhang1, Xiaoya Fu1, Xiangyang Zhang3, Bing Lang1, Xiaojun Xiang4, Wei Hao5. 1. Mental Health Institute of the Second Xiangya Hospital, The China National Clinical Research Center for Mental Health Disorders, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, People's Republic of China. 2. Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. 3. Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA. 4. Mental Health Institute of the Second Xiangya Hospital, The China National Clinical Research Center for Mental Health Disorders, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, People's Republic of China. xiangxiaojun2013@163.com. 5. Mental Health Institute of the Second Xiangya Hospital, The China National Clinical Research Center for Mental Health Disorders, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, People's Republic of China. weihao57@csu.edu.cn.
Abstract
RATIONALE: Although alcohol use disorder and anxiety disorders are highly comorbid in humans, controversy remains regarding whether anxiety predisposes individuals to alcohol reward, and the relationship with neurokinin-1 receptor (NK1R) is unclear. OBJECTIVES: The objectives of the study are to investigate the association between anxiety-like behavior and alcohol-induced conditioned place preference (CPP) and to examine the effect of NK1R antagonist L-703,606 on this preference and levels of NK1R protein in different brain regions in adolescent mice. METHODS: The anxiety-like behavior of adolescent male C57BL/6 mice was assessed using the elevated plus maze (EPM) test, and the animals were then allocated into high-anxiety mouse (HAM) and low-anxiety mouse (LAM) groups based on the percent of open arm time (OT%). After the reinforcement of ethanol was established by alcohol-induced CPP (2 g/kg), NK1R expression was quantified in the hippocampus, prefrontal cortex, and amygdala. Finally, the effect of L-703,606 (10 mg/kg) on the alcohol-induced CPP was examined. RESULTS: LAM showed a greater ethanol preference (P = 0.004) and a higher level of NK1R protein in the hippocampus (P = 0.026) than HAM group. Interestingly, the CPP score positively correlated with OT% (r = 0.520, P = 0.016) and the level of NK1R protein (r = 0.476, P = 0.029) in the hippocampus. Moreover, L-703,606 attenuated alcohol-induced CPP (P < 0.001) in both groups. CONCLUSIONS: The present results highlight the negative correlation between anxiety-like behavior and the propensity for alcohol and the critical role for NK1R in alcohol reward in adolescent mice. Importantly, the NK1R antagonist L-703,606 might be a promising therapeutic target for alcohol use disorder.
RATIONALE: Although alcohol use disorder and anxiety disorders are highly comorbid in humans, controversy remains regarding whether anxiety predisposes individuals to alcohol reward, and the relationship with neurokinin-1 receptor (NK1R) is unclear. OBJECTIVES: The objectives of the study are to investigate the association between anxiety-like behavior and alcohol-induced conditioned place preference (CPP) and to examine the effect of NK1R antagonist L-703,606 on this preference and levels of NK1R protein in different brain regions in adolescent mice. METHODS: The anxiety-like behavior of adolescent male C57BL/6 mice was assessed using the elevated plus maze (EPM) test, and the animals were then allocated into high-anxietymouse (HAM) and low-anxietymouse (LAM) groups based on the percent of open arm time (OT%). After the reinforcement of ethanol was established by alcohol-induced CPP (2 g/kg), NK1R expression was quantified in the hippocampus, prefrontal cortex, and amygdala. Finally, the effect of L-703,606 (10 mg/kg) on the alcohol-induced CPP was examined. RESULTS:LAM showed a greater ethanol preference (P = 0.004) and a higher level of NK1R protein in the hippocampus (P = 0.026) than HAM group. Interestingly, the CPP score positively correlated with OT% (r = 0.520, P = 0.016) and the level of NK1R protein (r = 0.476, P = 0.029) in the hippocampus. Moreover, L-703,606 attenuated alcohol-induced CPP (P < 0.001) in both groups. CONCLUSIONS: The present results highlight the negative correlation between anxiety-like behavior and the propensity for alcohol and the critical role for NK1R in alcohol reward in adolescent mice. Importantly, the NK1R antagonist L-703,606 might be a promising therapeutic target for alcohol use disorder.
Entities:
Keywords:
Alcohol use disorder; Anxiety; Conditioned place preference; Neurokinin-1 receptor
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