Effects of adolescent social defeat on adult amphetamine-induced locomotion and corticoaccumbal dopamine release in male rats.
Effects of adolescent social defeat on adult amphetamine-induced locomotion and corticoaccumbal dopamine release in male rats.
复制标题
青少年社会失败对成年苯丙胺引起的运动和雄性大鼠皮质辅助多巴胺释放的影响。
DOI：
10.1016/j.neuropharm.2012.11.013
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发表时间：
2013-04
影响因子：
4.7
通讯作者：
Watt MJ
中科院分区：
文献类型：
--
作者：
Burke AR;Forster GL;Novick AM;Roberts CL;Watt MJ
中皮质边缘多巴胺系统的成熟发生在青春期，在此期间暴露于社会压力会导致包括药物滥用障碍在内的行为障碍。成年雄性大鼠在青春期反复遭受社会失败后，表现出内侧前额叶皮层基础多巴胺含量减少，急性安非他明治疗后皮质伏隔多巴胺区域多巴胺含量改变，安非他明反复治疗后安非他明条件性位置偏好增加。这种变化可能反映了安非他明诱导的皮层伏隔区细胞外多巴胺释放的改变。因此，我们使用体内微透析来同时测量先前失败的大鼠和对照组的内侧前额叶皮层和伏隔核核心内的细胞外多巴胺，这是对急性或重复（每天7次注射）安非他明（1.0 mg/kg）的反应。在进行多巴胺测量的前一天，还评估了急性/重复安非他明的运动反应。青少年失败增强了成人对急性安非他明的运动反应，这与安非他明诱导的内侧前额叶皮层多巴胺释放减弱呈负相关，但安非他明诱导的伏隔区多巴胺释放没有差异。然而，在先前失败的大鼠和对照组之间，反复服用安非他明的运动和皮质伏隔多巴胺反应是相同的。这些数据表明，青少年失败增强了对初始安非他明暴露的行为反应，这是前额叶皮层多巴胺活动减少的功能，这可能足以促进随后增强寻求与药物相关的线索。有趣的是，反复的安非他明治疗似乎使安非他明引起的运动和皮层多巴胺反应正常化，这在暴露于青春期社交失败的成年大鼠中观察到，这为治疗应激性多巴胺功能障碍提供了启示。
Maturation of mesocorticolimbic dopamine systems occurs during adolescence, and exposure to social stress during this period results in behavioral dysfunction including substance abuse disorders. Adult male rats exposed to repeated social defeat in adolescence exhibit reduced basal dopamine tissue content in the medial prefrontal cortex, altered dopamine tissue content in corticoaccumbal dopamine regions following acute amphetamine, and increased amphetamine conditioned place preference following repeated amphetamine treatment. Such changes may reflect altered amphetamine-induced extracellular dopamine release in the corticoaccumbal regions. Therefore, we used in vivo microdialysis to measure extracellular dopamine simultaneously within the medial prefrontal cortex and nucleus accumbens core of previously defeated rats and controls, in response to either acute or repeated (7 daily injections) of amphetamine (1.0 mg/kg). Locomotion responses to acute / repeated amphetamine were also assessed the day prior to taking dopamine measurements. Adolescent defeat potentiated adult locomotion responses to acute amphetamine, which was negatively correlated with attenuated amphetamine-induced dopamine release in the medial prefrontal cortex, but there was no difference in amphetamine-induced accumbal dopamine release. However, both locomotion and corticoaccumbal dopamine responses to repeated amphetamine were equivalent between previously defeated rats and controls. These data suggest adolescent defeat enhances behavioral responses to initial amphetamine exposure as a function of diminished prefrontal cortex dopamine activity, which may be sufficient to promote subsequently enhanced seeking of drug-associated cues. Interestingly, repeated amphetamine treatment appears to normalize amphetamine-elicited locomotion and cortical dopamine responses observed in adult rats exposed to adolescent social defeat, providing implications for treating stress-induced dopamine dysfunction.
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