Bertrand E, Smadja C, Mauborgne A, Roques B P, Daugé V
Département de Pharmacochimie Moléculaire et Structurale, U266 INSERM, URA D1500 CNRS, UER des Sciences Pharmaceutiques et Biologiques, Paris, France.
Neuroscience. 1997 Sep;80(1):17-20. doi: 10.1016/s0306-4522(97)00136-x.
Chronic application of various mild stress has been shown to decrease the responsiveness to reward in rats. This effect, which was suggested to mimic anhedonia, one of the main symptoms observed in depressive patients, can be measured by various tests. Thus chronic mild stress was shown to reduce the consumption of a palatable sucrose solution, and to decrease the acquisition of preferences for a distinct environment paired with a variety of reinforcing substances. These negative responses could be prevented by chronic treatment with tricyclic or atypical antidepressants. The behavioural changes, induced by exposure to chronic mild stress, were shown to be associated with a number of changes in dopaminergic neurotransmission in the mesolimbic system, especially in the nucleus accumbens. The nucleus accumbens contains a large number of enkephalinergic cell bodies giving rise to local collaterals and axons projecting to the globus pallidus-ventral pallidum region (for review see Ref. 9). Furthermore, there is evidence that this structure is instrumental in mediating the reward effects of exogenous and endogenous opioids (for reviews see Refs 5,7,17). This study was carried out to analyse the possible contribution of the enkephalinergic system in the anhedonic-like state induced by chronic mild stress. Microdialysis was used to study the extracellular levels of [Met]enkephalin-like material in the rostral part of the nucleus accumbens of freely moving rats exposed or not to chronically mild stress. In both groups, the basal levels of [Met]enkephalin-like material were found to be similar. Exposure of the two groups to a congener, increased the extracellular levels of [Met]enkephalin in the controls but not in chronic mild stressed rats. This suggests that the reactivity of the endogenous opioid system could be reduced in stress induced model of anhedonia.
研究表明，长期施加各种轻度应激会降低大鼠对奖励的反应性。这种效应被认为模拟了快感缺失，而快感缺失是抑郁症患者主要症状之一，可通过各种测试来衡量。因此，长期轻度应激会减少美味蔗糖溶液的摄入量，并降低对与各种强化物质配对的独特环境的偏好习得。三环类或非典型抗抑郁药的长期治疗可预防这些负面反应。长期轻度应激引起的行为变化与中脑边缘系统，尤其是伏隔核中多巴胺能神经传递的一些变化有关。伏隔核包含大量脑啡肽能细胞体，这些细胞体产生局部侧支和投射到苍白球 - 腹侧苍白球区域的轴突（综述见参考文献9）。此外，有证据表明该结构在介导外源性和内源性阿片类药物的奖励效应中起作用（综述见参考文献5、7、17）。本研究旨在分析脑啡肽能系统在慢性轻度应激诱导的类快感缺失状态中的可能作用。采用微透析技术研究自由活动的大鼠在暴露或未暴露于慢性轻度应激的情况下，伏隔核前部细胞外[甲硫氨酸]脑啡肽样物质的水平。在两组中，发现[甲硫氨酸]脑啡肽样物质的基础水平相似。给两组大鼠注射一种同系物后，对照组中细胞外[甲硫氨酸]脑啡肽水平升高，而慢性轻度应激大鼠中则没有升高。这表明在内源性阿片系统应激诱导的快感缺失模型中，其反应性可能降低。
