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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Pharmacodynamic and receptor binding changes during chronic lorazepam administration.
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Pharmacodynamic and receptor binding changes during chronic lorazepam administration.

机译：慢性劳拉西m给药期间药效学和受体结合发生变化。

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摘要

To assess pharmacodynamic and neurochemical aspects of tolerance, lorazepam (2 mg/kg/day), or vehicle was administered chronically to male Crl: CD-1(ICR)BR mice via implantable osmotic pump. Open-field behavior, benzodiazepine receptor binding in vitro, receptor autoradiography, and muscimol-stimulated chloride uptake were examined at both 1 and 14 days. Open-field activity was depressed in lorazepam-treated animals on Day 1. On Day 14, open-field parameters were indistinguishable from those of vehicle-treated animals, indicating behavioral tolerance. Benzodiazepine binding, as determined by the specific binding of [125I]diazepam, was also decreased in cortex on Day 14. Hippocampal binding was unchanged following chronic lorazepam exposure. Apparent affinity in cortical membrane preparations was unchanged, indicating that altered ligand uptake was due to decreased receptor number. Muscimol-stimulated chloride uptake into cortical synaptoneurosomes from lorazepam-treated animals was not significantly different on Day 1 or Day 14 compared to vehicle-treated animals. These results confirm that down-regulation of benzodiazepine receptor binding is closely associated with behavioral tolerance to benzodiazepines. These observed changes in binding are not necessarily associated with robust changes in receptor function.
机译：为了评估耐受性的药效学和神经化学方面，通过植入式渗透泵向雄性Crl：CD-1（ICR）BR小鼠长期施用劳拉西m（2 mg / kg /天）或赋形剂。在第1天和第14天检查了开放视野行为，体外苯并二氮杂receptor受体结合，受体放射自显影以及麝香酚刺激的氯摄取。在第1天，接受劳拉西m治疗的动物的野外活动受到抑制。在第14天，野外参数与经媒介物处理的动物没有区别，表明其行为耐受性。由[125I]地西p的特异性结合确定的苯并二氮杂binding结合在第14天在皮质中也降低了。慢性劳拉西m暴露后海马结合没有改变。皮质膜制剂中的表观亲和力没有变化，表明配体摄取的改变是由于受体数目减少所致。与接受媒介物处理的动物相比，在接受劳拉西treated治疗的动物的皮层突触神经小体中，由麝香酚刺激的氯化物摄取在第1天或第14天没有显着差异。这些结果证实，苯二氮卓受体结合的下调与对苯二氮卓的行为耐受性密切相关。这些观察到的结合变化不一定与受体功能的强劲变化相关。

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