Effects of diazepam on behavioural and antinociceptive responses to the elevated plus-maze in male mice depend upon treatment regimen and prior maze experience
Effects of diazepam on behavioural and antinociceptive responses to the elevated plus-maze in male mice depend upon treatment regimen and prior maze experience
复制标题
地西泮对雄性小鼠高架十字迷宫的行为和抗伤害反应的影响取决于治疗方案和先前的迷宫经验
DOI：
10.1007/bf02253596
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发表时间：
2005
影响因子：
3.4
通讯作者：
J. Shepherd
中科院分区：
文献类型：
--
作者：
R. Rodgers;C. Lee;J. Shepherd
最近的研究表明，短暂暴露于高架十字迷宫（ESTA）产生非阿片类镇痛作用的雄性小鼠。本实验旨在评估地西泮对这种现象的影响。当急性给药时，低剂量（0.5-1.0 mg/kg）地西泮未能产生抗焦虑作用，并且对EPM诱导的甩尾潜伏期升高产生了相当不一致的影响。在经历过EPM的小鼠中，长期给予较高剂量的地西泮（2-4 mg/kg，8天）产生了较弱的抗焦虑作用，仅抑制了抗伤害感受的早期阶段。然而，在未接受过EP治疗的小鼠中，8天地西泮预处理具有显着的抗焦虑作用，并完全消除了对迷宫的抗伤害反应。总之，这些数据支持这样的观点，即焦虑是某些形式的适应性疼痛抑制的关键因素，并建议苯二氮卓类受体可能的介导作用。我们的研究结果还表明，事先暴露于麻醉剂，而不是长期处理/注射，大大降低了地西泮的抗焦虑作用。此外，由于再次暴露于迷宫本身减少了在开放臂和中央平台上花费的时间，因此行为基线的变化（“重新测试焦虑发生”）可能导致地西泮对试验动物的弱行为影响。重要的是，由于长期使用地西泮治疗并不影响这种焦虑样的复检特征，我们的数据表明，一个单一的既往经验的焦虑可能会从根本上改变这种测试引起的焦虑反应的性质。
Recent studies have shown that brief exposure to an elevated plus-maze (EPM) produces non-opioid antinociception in male mice. The present experiments were designed to assess the effects of diazepam on this phenomenon. When acutely administered, low doses (0.5–1.0 mg/kg) of diazepam failed to produce an anxiolytic profile and exerted rather inconsistent effects on EPM-induced elevations in tail-flick latencies. In EPM-experienced mice, chronic treatment with higher doses of diazepam (2–4 mg/kg, 8 days) produced a weak anxiolytic action and inhibited the early phase of EPM antinociception only. However, in EPM-naive mice, 8-day diazepam pretreatment exerted a marked anxiolytic effect and completely eliminated the antinociceptive response to the maze. Together, these data support the view that anxiety is a key factor in certain forms of adaptive pain inhibition and suggest a possible mediational role for benzodiazepine receptors. Our findings also show that prior exposure to the EPM, rather than chronic handling/injection, greatly reduces the anti-anxiety effect of diazepam. Furthermore, since re-exposure to the maze, perse, decreased time spent on the open arms and central platform, a shift in behavioural baseline (“retest anxiogenesis”) may have contributed to the weak behavioural effects of diazepam in test-experienced animals. Importantly, as chronic treatment with diazepam did not influence this anxiogenic-like retest profile, our data suggest that a single prior experience of the EPM may radically alter the nature of the anxiety reaction provoked by this test.