Doherty M D, Gratton A
Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montréal, Qué., Canada.
Brain Res. 1992 Jul 24;586(2):295-302. doi: 10.1016/0006-8993(92)91639-v.
The effects of repeated, once daily exposure to either restraint or tail pinch stress on extracellular levels of dopamine in nucleus accumbens and striatum were electrochemically monitored in conscious rats using high-speed chronoamperometry. Acutely, both tail pinch and restraint increased extracellular dopamine levels in both regions. However, the effect of restraint on mesolimbic and, to some extent, also on nigrostriatal dopamine neurotransmission increased progressively with each daily exposure. While increases in extracellular dopamine elicited by tail pinch varied across test days, no reliable daily enhancement of electrochemical responses to this stress were observed in either of the regions studied. Pretreatment with dopamine autoreceptor-specific doses of apomorphine (50 and 100 micrograms/kg s.c.) potently inhibited stress-elicited responses in nucleus accumbens, indicating that dopamine was the primary electroactive species contributing to the electrochemical signal. The results of this study indicate that the magnitude of stress-elicited increases in levels of extracellular dopamine is determined by the number of previous exposures to stress and are consistent with reports of sensitization to the behavioral effects of stress with repeated testing. The study also provides pharmacological data that are consistent with electrophysiological evidence of increased mesolimbic dopamine cell firing during exposure to stress.
采用高速计时电流法，对清醒大鼠反复每日一次暴露于束缚或夹尾应激下，伏隔核和纹状体细胞外多巴胺水平的影响进行电化学监测。急性情况下，夹尾和束缚均增加了两个区域的细胞外多巴胺水平。然而，束缚对中脑边缘系统以及在一定程度上对黑质纹状体多巴胺神经传递的影响，随着每日暴露次数的增加而逐渐增强。虽然夹尾引起的细胞外多巴胺增加在不同测试日有所变化，但在所研究的两个区域中均未观察到对这种应激的电化学反应有可靠的每日增强。用多巴胺自受体特异性剂量的阿扑吗啡（50和100微克/千克皮下注射）预处理可有效抑制伏隔核中应激引发的反应，表明多巴胺是构成电化学信号的主要电活性物质。本研究结果表明，应激引起的细胞外多巴胺水平升高的幅度取决于先前暴露于应激的次数，并且与反复测试对应激行为效应的敏化报道一致。该研究还提供了与应激期间中脑边缘多巴胺细胞放电增加的电生理证据一致的药理学数据。
