A chronic stress that impairs reactivity in rats also decreases dopaminergic transmission in the nucleus accumbens: A microdialysis study
A chronic stress that impairs reactivity in rats also decreases dopaminergic transmission in the nucleus accumbens: A microdialysis study
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DOI：
10.1046/j.1471-4159.1999.0722039.x
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发表时间：
1999-05-01
影响因子：
4.7
通讯作者：
De Montis, MG
中科院分区：
文献类型：
--
作者：
Gambarana, C;Masi, F;De Montis, MG
慢性应激诱导大鼠对伤害性刺激的反应性降低（逃避缺陷），这可以通过抗抑郁治疗逆转。目前的研究报告，这种情况下的行为缺陷是伴随着细胞外多巴胺的水平下降，在核壳。为了评估这一发现是否是减少释放或增强多巴胺的清除的结果，我们急性给药可卡因，2小时后d-安非他明，强调和控制大鼠。可卡因给药后，在应激动物中观察到的多巴胺输出量的增加显着低于对照大鼠中观察到的增加;而D-苯丙胺给药后释放的多巴胺总量在两组大鼠中相似。这些数据表明，多巴胺能神经元的活性降低可能是应激动物多巴胺基础水平降低的机制。有趣的是，应激组对可卡因的运动反应与对照组大鼠没有什么不同，因此表明对多巴胺受体刺激的敏感性。丙咪嗪管理每日伴随应激暴露完全恢复逃避赤字条件的慢性应激大鼠。此外，用丙咪嗪处理的应激大鼠显示出与对照动物中观察到的相似的基础和可卡因刺激的神经元多巴胺水平。
Chronic stress induces in rats a decreased reactivity toward noxious stimuli (escape deficit), which can be reverted by antidepressant treatments. The present study reports that this condition of behavioral deficit is accompanied by a decreased level of extracellular dopamine in the nucleus accumbens shell. To assess whether this finding was the result of a decreased release or of an enhanced removal of dopamine, we acutely administered cocaine, and 2 h later d-amphetamine, to stressed and control rats. The increases in dopamine output observed in stressed animals after cocaine administration were significantly lower than those observed in control rats; whereas the total amount of dopamine released after d-amphetamine administration was similar in both groups of rats. These data suggest a reduced activity of dopaminergic neurons as the possible mechanism underlying dopamine basal level reduction in stressed animals. It is interesting that the stress group showed a locomotor response to cocaine not different from control rats, thus suggesting a condition of sensitization to dopamine receptor stimulation. Imipramine administered daily concomitantly with stress exposure completely reverted the escape deficit condition of chronically stressed rats. Moreover, stressed rats treated with imipramine showed basal and cocaine stimulated levels of extraneuronal dopamine similar to those observed in control animals.