中脑边缘多巴胺能回路的发散异常可能与不同的抑郁行为有关，一项动物研究。
Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study.
机构信息
Medical Psychological Institute Second Xiangya Hospital Central South University Changsha Hunan China.
Mental Health Institute of The Second Xiangya Hospital Key Laboratory of Psychiatry and Mental Health of Hunan Province Central South University Changsha Hunan China.
出版信息
Brain Behav. 2017 Sep 8;7(10):e00808. doi: 10.1002/brb3.808. eCollection 2017 Oct.
BACKGROUND
The mesocorticolimbic dopamine system, which originates from the ventral tegmental area (VTA) and projects primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy), plays a pivotal role in determining individual motivation and sensitivity to rewards, namely, anhedonia. Not all depressive individuals exhibited anhedonia, thus, it is natural to speculate that the heterogenous manifestations of depression might be related to the mesocorticolimbic dopamine system. Maternal deprivation (MD) and chronic unpredictable stress (CUPS) are two well-established depressogenic stressors, and they were proven to induce different depressive phenotypes.
METHODS
The depressive and anxiety-like behaviors of MD and CUPS-treated rats were measured by classical behavioral tests including open field, forced swimming, and sucrose preference test. The expression of D1-5 dopamine receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system of rats exposed to MD and CUPS were measured by real-time PCR and Western blot, respectively.
RESULTS
Severe anhedonia was observed in MD but not CUPS rats. Divergent expression of D1 and D2 receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system were found between MD and CUPS rats. Significant correlations between different depressive behaviors and D1-/D2-like receptors and DAT protein levels in the mesocorticolimbic dopamine system were observed.
CONCLUSION
Different depressive behaviors of rats such as anhedonia, passive coping behavior, and declined exploratory interest might be related to divergent dopaminergic pathways. Anhedonia is associated with the dysfunction of VTA-NAc and VTA-OT dopaminergic pathways, the passive coping behavior is related to the dysregulation of VTA-PFC and VTA-AMy pathways, and individual exploratory interest is associated with abnormal activity of VTA-PFC and VTA-ST pathways.
背景
起源于腹侧被盖区（VTA）并主要投射到前额叶皮层（PFC）、嗅结节（OT）、伏隔核（NAc）、背侧纹状体（ST）和杏仁核（AMy）的中脑边缘多巴胺系统在决定个体动机和对奖励的敏感性方面起着关键作用，即快感缺失。并非所有抑郁个体都表现出快感缺失，因此，人们自然会推测抑郁的异质表现可能与中脑边缘多巴胺系统有关。母婴分离（MD）和慢性不可预测应激（CUPS）是两种已确立的致抑郁应激源，它们被证明会导致不同的抑郁表型。
方法
通过经典行为测试，包括旷场试验、强迫游泳试验和糖水偏好试验，测量 MD 和 CUPS 处理大鼠的抑郁和焦虑样行为。通过实时 PCR 和 Western blot 分别测量 MD 和 CUPS 暴露大鼠中脑边缘多巴胺系统中 D1-5 多巴胺受体和 DAT mRNA 和蛋白的表达。
结果
在 MD 大鼠中观察到严重的快感缺失，但在 CUPS 大鼠中没有观察到。在 MD 和 CUPS 大鼠中发现中脑边缘多巴胺系统中 D1 和 D2 受体和 DAT mRNA 和蛋白的表达存在差异。在中脑边缘多巴胺系统中，不同的抑郁行为与 D1-/D2 样受体和 DAT 蛋白水平之间存在显著相关性。
结论
大鼠的不同抑郁行为，如快感缺失、被动应对行为和探索兴趣下降，可能与多巴胺能途径的不同有关。快感缺失与 VTA-NAc 和 VTA-OT 多巴胺能途径的功能障碍有关，被动应对行为与 VTA-PFC 和 VTA-AMy 途径的失调有关，个体探索兴趣与 VTA-PFC 和 VTA-ST 途径的异常活动有关。
Zotero 插件