Roles of BDNF, dopamine D3 receptors, and their interactions in the expression of morphine-induced context-specific locomotor sensitization
Roles of BDNF, dopamine D3 receptors, and their interactions in the expression of morphine-induced context-specific locomotor sensitization
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DOI：
10.1016/j.euroneuro.2010.12.006
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发表时间：
2011-11-01
影响因子：
5.6
通讯作者：
Li, Yingcong
中科院分区：
文献类型：
--
作者：
Liang, Jing;Zheng, Xigeng;Li, Yingcong
环境刺激可以引发药物寻求、渴望和复吸，环境刺激通过与药物作用的反复关联而获得显着的动机。先前的研究表明，多巴胺D-3受体（Drd3）可能参与大鼠药物条件反应的表达，脑源性神经营养因子（BDNF）可以调节伏隔核（NAc）中Drd3的表达。然而，神经区域与 Drd3 激活的关系以及 BDNF 和 Drd3 之间在药物相关环境控制的行为反应表达中的潜在相互作用仍然知之甚少。本研究使用调节程序来评估 BDNF、Drd3 的作用以及它们在 NAc 中在吗啡诱导的上下文特异性运动敏化表达中的相互作用。我们发现吗啡配对环境中运动敏化的表达伴随着 Drd3 mRNA 和 BDNF mRNA 和蛋白水平的显着增加。吗啡配对大鼠的敏化运动和增强的 Drd3 mRNA 均被 NAc 内输注抗酪氨酸激酶受体 B (TrkB) IgG 所抑制。此外，NAc 内输注 Drd3 选择性拮抗剂 SB-277011A 显着降低了上下文特异性运动敏化的表达并上调了 BDNF mRNA。总而言之，这些结果表明 BDNF/TrkB 信号传导和 NAc 中 Drd3 的激活是吗啡诱导的上下文特异性运动敏化表达所必需的。 (C) 2011 Elsevier B.V. 和 ECNP。版权所有。
Drug seeking, craving, and relapse can be triggered by environmental stimuli that acquire motivational salience through repeated associations with the drug's effects. Previous studies indicated that the dopamine D-3 receptor (Drd3) might be involved in the expression of drug-conditioned responses in rats, and brain-derived neurotrophic factor (BDNF) could modulate Drd3 expression in the nucleus accumbens (NAc). However, the involvement of neural regions with Drd3 activation and the underlying interaction between BDNF and Drd3 in the expression of behavioral responses controlled by a drug-associated environment have remained poorly understood. The present study used a conditioning procedure to assess the roles of BDNF, Drd3, and their interactions in the NAc in the expression of morphine-induced context-specific locomotor sensitization. We showed that the expression of locomotor sensitization in the morphine-paired environment was accompanied by significantly increased expression of Drd3 mRNA and BDNF mRNA and protein levels. Both sensitized locomotion in morphine-paired rats and enhanced Drd3 mRNA were suppressed by intra-NAc infusion of anti-tyrosine kinase receptor B (TrkB) IgG. Furthermore, intra-NAc infusion of the Drd3-selective antagonist SB-277011A significantly decreased the expression of context-specific locomotor sensitization and upregulated BDNF mRNA. Altogether, these results suggest that BDNF/TrkB signaling and activation of Drd3 in the NAc are required for the expression of morphine-induced context-specific locomotor sensitization. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.