Institute of Physiology, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic.
Faculty of Science, Charles University, 12800 Prague, Czech Republic.
Int J Mol Sci. 2020 Apr 30;21(9):3184. doi: 10.3390/ijms21093184.
Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life; however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP; 1 mg/kg/day) in 7-11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms. Using RT-PCR and quantitative autoradiography, we examined the expression of the selected GABA receptor subunits (α1, α2, α4, γ2, and δ) and the GABA B2 subunit, and GABA, benzodiazepine, and GABA receptor binding 48 h, 1 week, and 2 months after treatment discontinuation. Within one week after CZP cessation, the expression of the α2 subunit was upregulated, whereas that of the δ subunit was downregulated in both the hippocampus and cortex. In the hippocampus, the α4 subunit was downregulated after the 2-month interval. Changes in receptor binding were highly dependent on the receptor type, the interval after treatment cessation, and the brain structure. GABA receptor binding was increased in almost all of the brain structures after the 48-h interval. BZD-binding was decreased in many brain structures involved in the neuronal networks associated with emotional behavior, anxiety, and cognitive functions after the 2-month interval. Binding of the GABA receptors changed depending on the interval and brain structure. Overall, the described changes may affect both synaptic development and functioning and may potentially cause behavioral impairment.
苯二氮䓬类药物（BZDs）在各个年龄段的患者中广泛使用。与成年人不同，接受 BZDs 治疗的新生动物在以后的生活中会表现出多种行为缺陷；然而，这些缺陷的机制尚未得到很好的理解。本研究旨在检查 7-11 日龄大鼠给予氯硝西泮（CZP；1mg/kg/天）是否会在短期和长期内影响γ-氨基丁酸（GABA）能受体。使用 RT-PCR 和定量放射自显影术，我们检查了选定的 GABA 受体亚基（α1、α2、α4、γ2 和 δ）和 GABA B2 亚基的表达，以及 GABA、苯二氮䓬和 GABA 受体结合在治疗停止后 48 小时、1 周和 2 个月的情况。在 CZP 停止后一周内，α2 亚基在海马体和皮质中的表达上调，而 δ 亚基的表达下调。在 2 个月的间隔后，海马体中的α4 亚基下调。受体结合的变化高度依赖于受体类型、治疗停止后的间隔和脑结构。在 48 小时的间隔后，几乎所有脑结构中的 GABA 受体结合增加。在 2 个月的间隔后，与情绪行为、焦虑和认知功能相关的神经元网络涉及的许多脑结构中，BZD 结合减少。GABA 受体结合根据间隔和脑结构而变化。总的来说，所描述的变化可能会影响突触的发育和功能，并可能潜在地导致行为障碍。
