CHRONIC ANTIDEPRESSANT ADMINISTRATION DECREASES THE EXPRESSION OF TYROSINE-HYDROXYLASE IN THE RAT LOCUS-CERULEUS
CHRONIC ANTIDEPRESSANT ADMINISTRATION DECREASES THE EXPRESSION OF TYROSINE-HYDROXYLASE IN THE RAT LOCUS-CERULEUS
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DOI：
10.1073/pnas.87.19.7522
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发表时间：
1990-10-01
影响因子：
11.1
通讯作者：
DUMAN, RS
中科院分区：
文献类型：
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作者：
NESTLER, EJ;MCMAHON, A;DUMAN, RS
在蓝斑（LC），大脑中的主要去甲肾上腺素能核，酪氨酸羟化酶表达的调节抗抑郁治疗进行了研究。用各种抗抑郁药对大鼠进行慢性治疗，并通过免疫印迹分析测定LC中的酪氨酸羟化酶水平。抗抑郁药物的所有主要类别的代表，包括丙咪嗪，去甲替林，反苯环丙胺，氟伏沙明，氟西汀，安非他酮，异吲哚，和电惊厥药物，被发现降低水平的酪氨酸羟化酶免疫反应性的40-70%，在LC。酶免疫反应性水平的降低与酶mRNA水平的同等降低相关。LC酪氨酸羟化酶的抗抑郁调节似乎是这些化合物所特有的，因为用其他类别的精神药物（包括氟哌啶醇、地西泮、可乐定、可卡因和吗啡）的代表对大鼠进行长期治疗，未能降低这种蛋白质的水平。结果表明，慢性抗抑郁药显着下调酪氨酸羟化酶的表达在LC和提高的可能性，这种调节的酶代表了适应性反应的LC神经元的抗抑郁药，介导他们的一些治疗作用，抑郁症和/或其他精神障碍。
Regulation of tyrosine hydroxylase expression by antidepressant treatments was investigated in the locus coeruleus (LC), the major noradrenergic nucleus in brain. Rats were treated chronically with various antidepressants, and tyrosine hydroxylase levels were measured in the LC by immunoblot analysis. Representatives of all major classes of antidepressant medication-including imipramine, nortriptyline, tranylcypromine, fluvoxamine, fluoxetine, bupropion, iprindole, and electroconvulsive seizures-were found to decrease levels of tyrosine hydroxylase immunoreactivity by 40-70% in the LC. Decreased levels of enzyme immunoreactivity were shown to be associated with equivalent decreases in enzyme mRNA levels. Antidepressant regulation of LC tyrosine hydroxylase appeared specific to these compounds, inasmuch as chronic treatment of rats with representatives of other classes of psychotropic drugs, including haloperidol, diazepam, clonidine, cocaine, and morphine, failed to decrease levels of this protein. The results demonstrate that chronic antidepressants dramatically downregulate the expression of tyrosine hydroxylase in the LC and raise the possibility that such regulation of the enzyme represents an adaptive response of LC neurons to antidepressants that mediates some of their therapeutic actions in depression and/or other psychiatric disturbances.