Hascoët M, Bourin M
Department of Pharmacology and GIS Médicament, Faculty of Medicine, Nantes, France.
Pharmacol Biochem Behav. 1997 Feb;56(2):317-24. doi: 10.1016/s0091-3057(96)00293-6.
A comparative study between two drugs acting on the GABAA receptor, alprazolam and alpidem was undertaken, using simple tests such as measurement of spontaneous locomotor activity, four plates test and rotarod in mice. Additional conflict test was further performed using a new conflict paradigm where the opportunity existed for rats to choose during punished periods between immediate, punished reinforcement and delayed non-punished reinforcement. The benzodiazepine alprazolam, demonstrated, as expected, strong anxiolytic effects in mice and increased punished response in rats at non sedative doses (0.5, 1 mg/kg). High doses of alprazolam decreased spontaneous locomotor activity and induced myorelaxant effects in mice. Alpidem, an imidazopyridine derivative, induced motor impairment in mice and only very weak anxiolytic effects in the four plates test in mice (4 mg/kg) and in punished procedure in rats (32 mg/kg). As alprazolam is a full agonist for the GABAA receptor complex and alpidem is a partial agonist acting with specificity on omega 1 GABAA receptor subtypes, the results are discussed. Activity on omega 1 receptor subtypes is perhaps not sufficient in order to obtain a true anti-conflict effect and compounds such as alpidem only relieve some of the symptoms of anxiety disorders.
使用简单的试验，如测量小鼠的自发运动活性、四板试验和转棒试验，对作用于GABAA受体的两种药物阿普唑仑和阿吡坦进行了一项比较研究。使用一种新的冲突范式进一步进行了额外的冲突试验，在该范式中，大鼠在受罚期间有机会在即时受罚强化和延迟非受罚强化之间进行选择。苯二氮䓬类药物阿普唑仑在非镇静剂量（0.5、1mg/kg）下，如预期所示，在小鼠中表现出强烈的抗焦虑作用，并增加了大鼠的受罚反应。高剂量的阿普唑仑降低了小鼠的自发运动活性，并诱导了肌肉松弛作用。阿吡坦是一种咪唑吡啶衍生物，在小鼠中诱导运动障碍，在小鼠的四板试验（4mg/kg）和大鼠的受罚程序（32mg/kg）中仅表现出非常微弱的抗焦虑作用。由于阿普唑仑是GABAA受体复合物的完全激动剂，而阿吡坦是对ω1 GABAA受体亚型具有特异性作用的部分激动剂，因此对结果进行了讨论。对ω1受体亚型的活性可能不足以获得真正的抗冲突效果，像阿吡坦这样的化合物只能缓解焦虑症的一些症状。
