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首页> 外文期刊>The European Journal of Neuroscience >The unique psychostimulant profile of (+/-)-modafinil: investigation of behavioral and neurochemical effects in mice
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The unique psychostimulant profile of (+/-)-modafinil: investigation of behavioral and neurochemical effects in mice

机译：（+/-） - modafinil的独特精神疗法概况：对小鼠的行为和神经化学作用的调查

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摘要

Blockade of dopamine (DA) reuptake via the dopamine transporter (DAT) is a primary mechanism identified as underlying the therapeutic actions of (+/-)-modafinil (modafinil) and its R-enantiomer, armodafinil. Herein, we explored the neurochemical and behavioral actions of modafinil to better characterize its psychostimulant profile. Swiss-Webster mice were implanted with microdialysis probes in the nucleus accumbens shell (NAS) or core (NAC) to evaluate changes in DA levels related to acute reinforcing actions of drugs of abuse. Additionally, subjective effects were studied in mice trained to discriminate 10mg/kg cocaine (i.p.) from saline. Modafinil (17-300mg/kg, i.p.) significantly increased NAS and NAC DA levels that at the highest doses reached similar to 300% at 1h, and lasted >6h in duration. These elevated DA levels did not show statistically significant regional differences between the NAS and NAC. Modafinil produced cocaine-like subjective effects at 56-100mg/kg when administered at 5 and 60min before the start of the session, and enhanced cocaine effects when the two were administered in combination. Despite sharing subjective effects with cocaine, modafinil's psychostimulant profile was unique compared to that of cocaine and like compounds. Modafinil had lower potency and efficacy than cocaine in stimulating NAS DA. In addition, the cocaine-like subjective effects of modafinil were obtained at lower doses and earlier onset times than expected based on its dopaminergic effects. These studies suggest that although inhibition of DA reuptake may be a primary mechanism underlying modafinil's therapeutic actions, non DA-dependent actions may be playing a role in its psychostimulant profile.
机译：通过多巴胺转运蛋白（DAT）阻断多巴胺（DA）再摄取是鉴定为（+/-） - Modafinil（Modafinil）及其R-映异构体，Armodafil的治疗作用的主要机制。在此，我们探讨了Modafinil的神经化学和行为作用，以更好地表征其精神疗法概况。将瑞士韦伯斯特小鼠植入细胞核壳（NAS）或核心（NAC）中的微透析探针，以评估与滥用药物急性增强作用相关的DA水平的变化。另外，在培训的小鼠中研究了主观效果，以区分盐水10mg / kg可卡因（I.p.）。 Modafinil（17-300mg / kg，i.p.）显着增加NAS和NAC DA水平，在最高剂量的达到达到的最高剂量下，持续时间为3小时，持续> 6小时。这些升高的DA水平没有显示NAS和NAC之间的统计学意义的区域差异。在会议开始前56-100mg / kg时，Mocafinil在56-100mg / kg时产生了可卡因的主观效果，并且当两者组合施用时增强的可卡因效应。尽管与可卡因共享主观效果，与可卡因和诸如化合物相比，Modafinil的精神疗法概况是独一无二的。 Mocafinil在刺激NAS DA中的可卡因具有较低的效力和功效。此外，基于其多巴胺能效应，在较低剂量和早先的发病时间下获得Mocafinil的可卡因的主观效果。这些研究表明，尽管DA再摄取的抑制可以是Modafinil的治疗作用的主要机制，但非DA依赖性动作可能在其精神疗法概况中发挥作用。

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