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阻断伏隔核中 ERK 的磷酸化可抑制可卡因诱导的大鼠行为敏化的表达。

Blockade of ERK Phosphorylation in the Nucleus Accumbens Inhibits the Expression of Cocaine-induced Behavioral Sensitization in Rats.

机构信息

Department of Physiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.

出版信息

Korean J Physiol Pharmacol. 2011 Dec;15(6):389-95. doi: 10.4196/kjpp.2011.15.6.389. Epub 2011 Dec 27.

DOI:10.4196/kjpp.2011.15.6.389
PMID:22359477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3282227/
Abstract

Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or 2.0µ g/side), or U0126 (0.1 or 1.0µg/side), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 (2.0µ g/side) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-induced behavioral sensitization, and further suggest that repeated cocaine evokes neuronal plasticity involving ERK pathway in this site leading to long-lasting behavioral changes.

摘要

反复给予可卡因等精神兴奋剂会导致行为敏感化的发展。细胞外信号调节激酶（ERK）是一种对长期神经元可塑性很重要的酶，它与这些药物的作用有关。虽然伏隔核（NAcc）是介导药物滥用引起的行为敏感化表达的部位，但 ERK 激活在该部位的确切作用尚未确定。在这项研究中，我们证明了通过单次双侧微注射 PD98059（0.5 或 2.0μg/侧）或 U0126（0.1 或 1.0μg/侧）到该部位，ERK 磷酸化的阻断可剂量依赖性地抑制可卡因诱导的行为敏感化的表达，当在 6 次连续每日可卡因注射（15mg/kg，ip）后第 7 天测量时。与生理盐水对照相比，急性微注射载体或 PD98059 本身不会产生不同的运动活性。此外，NAcc 中 PD98059（2.0μg/侧）的微注射特异性降低了该部位可卡因诱导的 ERK 磷酸化水平的增加，而不影响 p-38 蛋白水平。这些结果表明，NAcc 中的 ERK 激活是可卡因诱导的行为敏感化表达所必需的，进一步表明，反复给予可卡因会引起该部位涉及 ERK 途径的神经元可塑性，从而导致持久的行为变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/9ceba4275a28/kjpp-15-389-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/7c337ac27d98/kjpp-15-389-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/5e2ec4f5a0b0/kjpp-15-389-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/d416f174dc3f/kjpp-15-389-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/9ceba4275a28/kjpp-15-389-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/7c337ac27d98/kjpp-15-389-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/5e2ec4f5a0b0/kjpp-15-389-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/d416f174dc3f/kjpp-15-389-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d1/3282227/9ceba4275a28/kjpp-15-389-g004.jpg

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