Dopamine receptor D1 but not D3 essential for morphine-induced conditioned responses.
Dopamine receptor D1 but not D3 essential for morphine-induced conditioned responses.
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DOI：
10.4238/2015.january.16.1
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发表时间：
2015-01
期刊：
影响因子：
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通讯作者：
Y. Wang;S. Wei;Y. Zhu;B. Zhao;X. Xun;J. Lai
中科院分区：
文献类型：
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作者：
Y. Wang;S. Wei;Y. Zhu;B. Zhao;X. Xun;J. Lai
最近的研究表明，多巴胺受体D1和D3参与调节小鼠对吗啡的运动兴奋和条件反应。此外，脑源性神经营养因子（BDNF）的表达可能是由D1和D3受体活动在脑桥核（NAc）和前额叶皮层（PFC）的调制。然而，D1和D3受体与BDNF在药物相关线索控制的行为反应表达中的潜在相互作用尚未完全阐明。在这项研究中，我们使用多巴胺受体突变小鼠，以探讨D1和D3受体在运动和吗啡诱导的位置偏爱的作用，此外，我们研究了吗啡对BDNF表达的小鼠大脑NAc和PFC的影响。我们的研究结果表明，D1受体而不是D3受体突变小鼠对急性吗啡诱导（10 mg/kg）的运动敏感性降低（D1：3814.82 ± 319.9 cm vs D3：8089.64 ± 967.4 cm）。此外，D1受体突变小鼠没有获得吗啡条件性位置偏爱（D1：-18.3 ± 59.9，D3：217.7 ± 64.1），并显示NAc中BDNF表达减少与野生型和D3受体突变小鼠相比，D1：0.33 ± 0.07倍，D3：2.21 ± 0.18倍）和PFC（D1：0.74 ± 0.15倍，D3：1.68 ± 0.22倍）。这些研究结果表明，D1受体是必要的诱导线索相关的吗啡寻求和调节运动习惯化过程中响应急性吗啡。多巴胺受体D1而不是D3也是吗啡诱导的NAc和PFC中BDNF表达的关键。
Recent studies indicate the involvement of dopamine receptors D1 and D3 in the regulation of locomotor stimulant and conditioned responses to morphine in mice. Moreover, expression of brain-derived neurotrophic factor (BDNF) may be modulated by D1 and D3 receptor activities in the nucleus accumbens (NAc) and prefrontal cortex (PFC). However, the underlying interactions between D1 and D3 receptors and BDNF in the expression of behavioral responses controlled by drug-associated cues have not yet been fully elucidated. In this study, we used dopamine receptor mutant mice to explore the roles of the D1 and D3 receptors in locomotion and morphine-induced place preference; furthermore, we investigated the effects of morphine on BDNF expression in the NAc and PFC of the mouse brain. Our results show that D1 receptor but not D3 receptor mutant mice had decreased sensitivity to acute morphine-induced (10 mg/kg) locomotion (D1: 3814.82 ± 319.9 cm vs D3: 8089.64 ± 967.4 cm). Furthermore, D1 receptor mutant mice did not acquire morphine-conditioned place preference (D1: -18.3 ± 59.9, D3: 217.7 ± 64.1) and showed decreased BDNF expression in the NAc (D1: 0.33 ± 0.07 fold, D3: 2.21 ± 0.18 fold) and PFC (D1: 0.74 ± 0.15 fold, D3: 1.68 ± 0.22 fold) compared with wild-type and D3 receptor mutant mice. These findings suggest that the D1 receptor is necessary for the induction of cue-associated morphine seeking and modulates locomotor habituation processes in response to acute morphine. The dopamine receptor D1 but not the D3 is also critical for morphine-induced BDNF expression in the NAc and PFC.