Tyrosine depletion attenuates dopamine function in healthy volunteers
Tyrosine depletion attenuates dopamine function in healthy volunteers
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DOI：
10.1007/s002130000613
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发表时间：
2001-02-01
影响因子：
3.4
通讯作者：
Cowen, PJ
中科院分区：
文献类型：
--
作者：
Harmer, CJ;McTavish, SFB;Cowen, PJ
理论基础：在动物和人类研究中，酪氨酸耗竭已被证明可以减少多巴胺的活性。然而，对基础多巴胺功能的影响还没有被探索。这些信息可以建立酪氨酸耗竭作为健康志愿者多巴胺功能的有效探针，也将对这种操作的未来治疗应用具有相关性。目的：采用神经内分泌、神经心理和主观测量相结合的方法，研究急性酪氨酸耗竭对健康志愿者多巴胺功能的影响。方法：志愿者一次饮用不含酪氨酸和苯丙氨酸的氨基酸饮料(不含酪氨酸和苯丙氨酸)，另一次饮用平衡(BAL)氨基酸饮料。在两杯饮料后的6小时内，志愿者们对血浆催乳素、氨基酸水平和主观状态进行了监测，志愿者们还完成了CANTAB的一系列测试，包括之前发现对多巴胺功能变化敏感的空间记忆测量。结果：与平衡混合物相比，不含TYR饮料后血浆催乳素水平升高，表明下丘脑内多巴胺神经传递减少。在喝了不含TYR的饮料后，志愿者的空间识别记忆和空间工作记忆受到了损害。志愿者也倾向于报告说，在服用不含TYR的BAL混合物后，他们感觉不如服用BAL混合物。结论：健康志愿者酪氨酸耗竭对基线多巴胺功能的影响与本研究采用的不同方法有关。因此，酪氨酸耗竭作为研究人类志愿者体内多巴胺功能的指标似乎很有价值。抑郁症的评分和认知功能的其他方面没有受到影响，这表明，当用于治疗以多巴胺过度活动为特征的疾病时，如急性躁狂症和精神分裂症，这种手法可能没有显著的副作用。
Rationale: Tyrosine depletion has been shown to reduce dopamine over activity in animal and human investigations. However, the effects on basal dopamine function have not been explored. Such information could establish tyrosine depletion as an effective probe of dopamine function in healthy volunteers and would also have relevance for future therapeutic applications of this manipulation. Objective: The present study investigated the effect of acute tyrosine depletion on dopamine function in healthy volunteers using a combination of neuroendocrine, neuropsychological and subjective measures. Methods: On one occasion, volunteers received an amino acid drink selectively lacking tyrosine and phenylalanine (TYR-free), whilst on the other they received a balanced (BAL) amino acid drink. Plasma prolactin, amino acid levels and subjective state were monitored over 6 h following the two drinks, and volunteers also completed a battery of tests from the CANTAB, including measures of spatial memory previously found to be sensitive to changes in dopamine function. Results: Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, indicative of decreased dopamine neurotransmission within the hypothalamus. Following the TYR-free drink, volunteers were impaired at spatial recognition memory and spatial working memory. Volunteers also tended to report that they felt less good following the TYR-free than the BAL mixture. Conclusion: Tyrosine depletion in healthy volunteers affected baseline dopamine function on the different measures employed in this study. Tyrosine depletion would thereby seem valuable as a probe of dopamine function in human volunteers. Ratings of depression and other aspects of cognitive function were unaffected, suggesting that this manipulation may be free of significant side effects when used as a treatment for conditions characterised by dopamine over activity, such as acute mania and schizophrenia.