Wisłowska-Stanek Aleksandra, Turzyńska Danuta, Sobolewska Alicja, Kołosowska Karolina, Szyndler Janusz, Skórzewska Anna, Maciejak Piotr
Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Banacha 1B, 02-097, Warszawa, Poland.
Department of Experimental and Clinical Neuroscience, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957, Warszawa, Poland.
Pharmacol Rep. 2024 Apr;76(2):348-367. doi: 10.1007/s43440-024-00573-w. Epub 2024 Mar 22.
The study aimed to assess the influence of a single valproate (VPA) administration on inhibitory and excitatory neurotransmitter concentrations in the brain structures involved in epileptogenesis in pentylenetetrazol (PTZ)-kindled rats.
Adult, male Wistar rats were kindled by repeated intraperitoneal (ip) injections of PTZ at a subconvulsive dose (30 mg/kg, three times a week). Due to the different times required to kindle the rats (18-22 injections of PTZ), a booster dose of PTZ was administrated 7 days after the last rats were kindled. Then rats were divided into two groups: acute administration of VPA (400 mg/kg) or saline given ip. The concentration of amino acids, kynurenic acid (KYNA), monoamines, and their metabolites in the prefrontal cortex, hippocampus, amygdala, and striatum was assessed by high-pressure liquid chromatography (HPLC).
It was found that a single administration of VPA increased the gamma-aminobutyric acid (GABA), tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and KYNA concentrations and decreased aspartate (ASP) levels in PTZ-kindled rats in the prefrontal cortex, hippocampus, amygdala and striatum.
Our results indicate that a single administration of VPA in the PTZ-kindled rats restored proper balance between excitatory (decreasing the level of ASP) and inhibitory neurotransmission (increased concentration GABA, KYNA) and affecting serotoninergic neurotransmission in the prefrontal cortex, hippocampus, amygdala, and striatum.
本研究旨在评估单次给予丙戊酸盐（VPA）对戊四氮（PTZ）点燃大鼠癫痫发生相关脑结构中抑制性和兴奋性神经递质浓度的影响。
成年雄性Wistar大鼠通过腹腔内（ip）重复注射亚惊厥剂量的PTZ（30mg/kg，每周三次）进行点燃。由于点燃大鼠所需时间不同（18 - 22次PTZ注射），在最后一只大鼠点燃后7天给予一次PTZ加强剂量。然后将大鼠分为两组：腹腔内急性给予VPA（400mg/kg）或生理盐水。通过高压液相色谱（HPLC）评估前额叶皮质、海马、杏仁核和纹状体中氨基酸、犬尿烯酸（KYNA）、单胺及其代谢物的浓度。
发现在PTZ点燃的大鼠中，单次给予VPA可增加前额叶皮质、海马、杏仁核和纹状体中γ-氨基丁酸（GABA）、色氨酸（TRP）、5-羟吲哚乙酸（5-HIAA）和KYNA的浓度，并降低天冬氨酸（ASP）水平。
我们的结果表明，在PTZ点燃的大鼠中单次给予VPA可恢复兴奋性（降低ASP水平）和抑制性神经传递（增加GABA、KYNA浓度）之间的适当平衡，并影响前额叶皮质、海马、杏仁核和纹状体中的5-羟色胺能神经传递。
