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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >One-trial tolerance to midazolam is due to enhancement of fear and reduction of anxiolytic-sensitive behaviors in the elevated plus-maze retest in the rat.
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One-trial tolerance to midazolam is due to enhancement of fear and reduction of anxiolytic-sensitive behaviors in the elevated plus-maze retest in the rat.

机译：对咪达唑仑的一次试验耐受性是由于大鼠中增强的迷宫复测中的恐惧感增强和抗焦虑敏感性行为降低所致。

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摘要

The anxiolytic-like effects of benzodiazepines (BZDs) in rats is reduced after a single exposure to the elevated plus-maze test (EPM). Several hypotheses have been formulated but no conclusive explanation exists for this phenomenon called "one-trial tolerance." In this study, we examined this phenomenon further by carrying out an ethopharmacological analysis of the behavior of rats submitted to the EPM in two trials. Rats injected with saline before both trials (control), treated with 1.0 mg/kg of midazolam before both trials (MM), or only before Trial 2 (SM), were exposed to the EPM. The SM group did not differ from the controls in the Trial 1 and Trial 2 conditions. The MM group showed a clear anxioselective profile in Trial 1 and no anxiolytic-like effects in Trial 2. Whereas midazolam injected before the first trial caused no significant change in immobility, there was a pronounced increase in immobility during Trial 2 for all three conditions. These data suggest that the anxiolytic-like action of midazolam in the first trial gives way to the fear-related insensitive behaviors (phobic/avoidance responses) responsible for the one-trial tolerance to BZDs in Trial 2. Furthermore, an additional experiment showed that midazolam does not seem to affect the acquisition of the learned avoidance response since it is present upon retesting even after midazolam administration in Trial 1 (MS group). Rather, the present data suggest an emotional shift from Trial 1 to Trial 2, which leads to change in the responsiveness of the animals to BZDs.
机译：一次暴露于高迷宫试验（EPM）后，苯二氮卓类（BZDs）对大鼠的抗焦虑作用降低。已经提出了几种假设，但对于这种现象，没有一个结论性的解释，即“一次试验的容忍度”。在这项研究中，我们通过两项试验对提交给EPM的大鼠的行为进行了药理学分析，进一步研究了这种现象。在两个试验之前（对照组），在两个试验之前（MM）或仅在第2次试验（SM）之前用1.0 mg / kg咪达唑仑治疗的大鼠均暴露于EPM中。 SM组在试验1和试验2的条件下与对照组无差异。 MM组在试验1中显示出明显的抗焦虑特性，在试验2中没有抗焦虑样作用。尽管在第一次试验之前注射的咪达唑仑没有引起固定性的明显变化，而在试验2中，所有这三种情况的固定性均明显增加。这些数据表明，在第一个试验中，咪达唑仑的抗焦虑样作用让位于与恐惧相关的不敏感行为（恐惧/回避反应），该行为导致试验2对BZD的单次耐受。此外，另一项实验表明咪达唑仑似乎不影响学习的回避反应的获得，因为即使在试验1（MS组）中给予咪达唑仑后，咪达唑仑仍会在重新测试时出现。而是，当前数据表明从试验1到试验2的情绪转变，这导致动物对BZD的反应能力发生变化。

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