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首页> 外文期刊>The European Journal of Neuroscience >Paradoxical effects of prodynorphin gene deletion on basal and cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens.
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Paradoxical effects of prodynorphin gene deletion on basal and cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens.

机译：前强啡肽基因缺失对伏伏核的基础和可卡因诱发的多巴胺能神经传递的悖论作用。

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Quantitative and conventional microdialysis were used to investigate the effects of constitutive deletion of the prodynorphin gene on basal dopamine (DA) dynamics in the nucleus accumbens (NAc) and the responsiveness of DA neurons to an acute cocaine challenge. Saline- and cocaine-evoked locomotor activity were also assessed. Quantitative microdialysis revealed that basal extracellular DA levels were decreased, while the DA extraction fraction, an indirect measure of DA uptake, was unchanged in dynorphin (DYN) knockout (KO) mice. The ability of cocaine to increase NAc DA levels was reduced in KO. Similarly, cocaine-evoked locomotor activity was decreased in KO. The selective kappa opioid receptor agonist U-69593 decreased NAc dialysate DA levels in wildtype mice and this effect was enhanced in KO. Administration of the selective kappa opioid receptor (KOPr) antagonist nor-binaltorphimine to KO mice attenuated the decrease in cocaine-induced DA levels. However, it was ineffective in altering the decreased locomotor response to cocaine. These studies demonstrate that constitutive deletion of prodynorphin is associated with a reduction of extracellular NAc DA levels and a decreased responsiveness to acute cocaine. Data regarding the effects of U-69593 and nor-binaltorphimine in KO suggest that the kappa opioid receptor is up-regulated as a consequence of prodynorphin gene deletion and that this adaptation underlies the decrease in basal DA dynamics and cocaine-evoked DA levels observed in DYN KO mice. These findings suggest that the phenotype of DYN KO mice is not solely due to loss of endogenous opioid peptide but also reflects developmental compensations that occur at the level of the opioid receptor.
机译：定量和常规微透析技术用于研究组成型缺失的强啡肽原基因对伏隔核（NAc）中基础多巴胺（DA）动力学的影响以及DA神经元对急性可卡因攻击的反应。还评估了盐水和可卡因诱发的自发活动。定量微透析显示，在强啡肽（DYN）敲除（KO）小鼠中，基础细胞外DA水平降低，而DA提取分数（间接摄取DA的指标）未发生变化。可卡因增加NAc DA水平的能力在KO中降低。同样，可卡因引起的运动活性在KO中降低。选择性κ阿片样物质受体激动剂U-69593降低了野生型小鼠的NAc透析液DA水平，并且在KO中这种作用得到增强。选择性κ阿片受体（KOPr）拮抗剂nor-binaltorphimine给予KO小鼠减缓了可卡因诱导的DA水平的降低。然而，它在改变对可卡因的运动反应降低方面无效。这些研究表明，强啡肽的组成型缺失与细胞外NAc DA水平的降低和对急性可卡因的响应性降低相关。有关U-69593和去甲倍他芬胺在KO中作用的数据表明，由于前强啡肽基因缺失，κ阿片受体被上调，这种适应作用是基础DA动力学和可卡因诱发的DA水平下降的基础。 DYN KO小鼠。这些发现表明，DYN KO小鼠的表型不仅是由于内源性阿片肽的丢失，而且还反映了在阿片受体水平发生的发育补偿。

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