Lopez F, Miller L G, Greenblatt D J, Schatzki A, Lumpkin M, Shader R I
Department of Pharmacology, Tufts University School of Medicine, Boston, Massachusetts.
J Clin Psychopharmacol. 1992 Apr;12(2):119-23.
After acute administration of low doses, alprazolam displays unusual behavioral and neurochemical characteristics. To determine whether chronic low-dose alprazolam has unique effects, we treated mice for 1-14 days with alprazolam 0.2 mg/kg per day and evaluated open-field activity, benzodiazepine receptor binding, t-butylbicyclophosphorothionate binding, and muscimol-stimulated chloride uptake. Open-field activity in treated mice was similar to that of control mice at each timepoint during alprazolam administration. Similarly, benzodiazepine receptor binding in vivo was unchanged in five brain regions. Benzodiazepine receptor binding in vivo was unchanged in five brain regions. Benzodiazepine binding in vitro in the cortex was unaffected by alprazolam treatment, as was t-butylbicyclophosphorothionate binding in the cortex. However, muscimol-stimulated chloride uptake was increased after 2 and 4 days of alprazolam compared with results after 1, 7, and 14 days. These results are consistent with prior reports of unusual effects of low-dose alprazolam and extend these findings to chronic administration.
急性给予低剂量阿普唑仑后，它会表现出不同寻常的行为和神经化学特征。为了确定慢性低剂量阿普唑仑是否有独特作用，我们每天用0.2毫克/千克阿普唑仑对小鼠进行1至14天的治疗，并评估旷场活动、苯二氮䓬受体结合、叔丁基双环磷硫代酸酯结合以及蝇蕈醇刺激的氯离子摄取。在阿普唑仑给药期间的每个时间点，接受治疗的小鼠的旷场活动与对照小鼠相似。同样，五个脑区的体内苯二氮䓬受体结合没有变化。皮质中的体外苯二氮䓬结合不受阿普唑仑治疗的影响，皮质中的叔丁基双环磷硫代酸酯结合也是如此。然而，与1、7和14天后的结果相比，阿普唑仑给药2天和4天后蝇蕈醇刺激的氯离子摄取增加。这些结果与先前关于低剂量阿普唑仑不同寻常作用的报道一致，并将这些发现扩展到慢性给药。
