Chronic morphine treatment increases cyclic AMP-dependent protein kinase activity in the rat locus coeruleus.
Chronic morphine treatment increases cyclic AMP-dependent protein kinase activity in the rat locus coeruleus.
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发表时间：
1988-02
影响因子：
3.6
通讯作者：
Eric J. Nestler;John F. Tallman
中科院分区：
文献类型：
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作者：
Eric J. Nestler;John F. Tallman
我们研究了环腺苷酸依赖性蛋白激酶在介导阿片成瘾的中枢神经系统中的可能作用，重点是大鼠蓝斑。这个脑区非常适合这些研究，因为它是相对同质的，因为丰富的电生理和行为数据表明，它在介导阿片类药物对动物（包括人类）的慢性影响方面发挥着重要作用。结果发现，慢性，但不是急性，在体内治疗的大鼠吗啡增加环腺苷酸依赖性蛋白激酶的活性在蓝斑的时间过程中，密切的蓝斑神经元成为耐受和依赖阿片类药物的时间过程，根据电生理学研究。同时给予阿片受体拮抗剂纳洛酮可阻断长期吗啡治疗对蛋白激酶活性的影响，表明该作用是通过特异性激活阿片受体介导的。相比之下，慢性吗啡治疗并没有改变其他几个大脑区域的蛋白激酶活性，包括新纹状体，额叶皮质和中缝背核。我们认为，所观察到的增加环腺苷酸依赖性蛋白激酶活性的蓝斑有助于阿片类药物成瘾的生化基础。
We have studied a possible role for cyclic AMP-dependent protein kinase in mediating opiate addiction in the central nervous system by focusing on the rat locus coeruleus. This brain region is well suited for these studies because it is relatively homogeneous and because a wealth of electrophysiological and behavioral data indicate that it plays an important role in mediating the chronic effects of opiates in animals, including humans. It was found that chronic, but not acute, in vivo treatment of rats with morphine increased cyclic AMP-dependent protein kinase activity in the locus coeruleus with a time course that closely paralleled the time course by which locus coeruleus neurons become tolerant to and dependent on opiates, based on electrophysiological studies. Concomitant administration of the opiate receptor antagonist naltrexone was found to block the effect of chronic morphine treatment on protein kinase activity, indicating that the effect is mediated via specific activation of opiate receptors. In contrast, chronic morphine treatment did not alter protein kinase activity in several other brain regions studied, including the neostriatum, frontal cortex, and dorsal raphe. We propose that the observed increase in cyclic AMP-dependent protein kinase activity in the locus coeruleus contributes to the biochemical basis of opiate addiction.