Department of Anatomy, Faculty of Medical Sciences in Katowice, Medical University of Silesia, ul. Medyków 18, 40-752, Katowice, Poland.
Department of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, ul. Medyków 18, 40-752, Katowice, Poland.
Pharmacol Rep. 2022 Aug;74(4):637-653. doi: 10.1007/s43440-022-00374-z. Epub 2022 Jun 2.
Neuropeptide S (NPS) is a multifunctional regulatory factor that exhibits a potent anxiolytic activity in animal models. However, there are no reports dealing with the potential molecular relationships between the anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs) and NPS signaling, especially in the context of novel stress-related neuropeptides action. The present work therefore focused on gene expression of novel stress neuropeptides in the rat brain after acute treatment with escitalopram and in combination with neuropeptide S receptor (NPSR) blockade.
Studies were carried out on adult, male Sprague-Dawley rats that were divided into five groups: animals injected with saline (control) and experimental rats treated with escitalopram (at single dose 10 mg/kg daily), escitalopram and SHA-68, a selective NPSR antagonist (at a single dose of 40 mg/kg), SHA-68 alone and corresponding vehicle (solvent SHA-68) control. To measure anxiety-like behavior and locomotor activity the open field test was performed. All individuals were killed under anaesthesia and the whole brain was excised. Total mRNA was isolated from homogenized samples of the amygdala, hippocampus, hypothalamus, thalamus, cerebellum, and brainstem. Real-time PCR was used for estimation of related NPS, NPSR, neuromedin U (NMU), NMU receptor 2 (NMUR2) and nesfatin-1 precursor nucleobindin-2 (NUCB2) gene expression.
Acute escitalopram administration affects the local expression of the examined neuropeptides mRNA in a varied manner depending on brain location. An increase in NPSR and NUCB2 mRNA expression in the hypothalamus and brainstem was abolished by SHA-68 coadministration, while NMU mRNA expression was upregulated after NPSR blockade in the hippocampus and cerebellum.
The pharmacological effects of escitalopram may be connected with local NPSR-related alterations in NPS/NMU/NMUR2 and nesfatin-1 gene expression at the level of selected rat brain regions. A novel alternative mode of SSRI action can be therefore cautiously proposed.
神经肽 S（NPS）是一种多功能调节因子，在动物模型中具有很强的抗焦虑活性。然而，目前尚无关于选择性 5-羟色胺再摄取抑制剂（SSRIs）的抗焦虑活性与 NPS 信号之间潜在分子关系的报道，特别是在新型应激相关神经肽作用的背景下。因此，本工作主要集中在急性给予依地普仑后大鼠大脑中新的应激神经肽的基因表达，以及与神经肽 S 受体（NPSR）阻断联合研究。
研究对象为成年雄性 Sprague-Dawley 大鼠，分为五组：注射生理盐水（对照组）和依地普仑（每日单次剂量 10mg/kg）、依地普仑和选择性 NPSR 拮抗剂 SHA-68（单次剂量 40mg/kg）、SHA-68 单独给药和相应溶剂（SHA-68 溶剂）对照组的实验大鼠。为了测量焦虑样行为和运动活性，进行了旷场测试。所有个体均在麻醉下处死，取出整个大脑。从杏仁核、海马体、下丘脑、丘脑、小脑和脑干匀浆样本中分离总 mRNA。实时 PCR 用于估计相关的 NPS、NPSR、神经肽 U（NMU）、NMU 受体 2（NMUR2）和 nesfatin-1 前体核结合蛋白 2（NUCB2）基因表达。
依地普仑的急性给药会根据大脑位置的不同，以不同的方式影响所检查神经肽 mRNA 的局部表达。在下丘脑和脑干中，NPSR 和 NUCB2 mRNA 表达的增加被 SHA-68 共同给药所消除，而在海马体和小脑中，NPSR 阻断后 NMU mRNA 表达上调。
依地普仑的药理作用可能与特定大鼠脑区 NPSR 相关的 NPS/NMU/NMUR2 和 nesfatin-1 基因表达改变有关。因此，可以谨慎地提出 SSRI 作用的新替代模式。
