The effect of valproate on the amino acids, monoamines, and kynurenic acid concentrations in brain structures involved in epileptogenesis in the pentylenetetrazol-kindled rats.

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Pharmacological Reports Pub Date : 2024-04-01 Epub Date: 2024-03-22 DOI:10.1007/s43440-024-00573-w
Aleksandra Wisłowska-Stanek, Danuta Turzyńska, Alicja Sobolewska, Karolina Kołosowska, Janusz Szyndler, Anna Skórzewska, Piotr Maciejak
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Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Abstract Image

丙戊酸钠对戊四唑诱发的大鼠大脑结构中涉及癫痫发生的氨基酸、单胺和犬尿氨酸浓度的影响。
研究背景本研究旨在评估单次服用丙戊酸钠(VPA)对戊四氮唑(PTZ)诱发的大鼠大脑结构中参与癫痫发生的抑制性和兴奋性神经递质浓度的影响:对成年雄性Wistar大鼠反复腹腔注射(ip)亚惊厥剂量的PTZ(30 mg/kg,每周三次)进行诱导。由于点燃大鼠所需的时间不同(注射 18-22 次 PTZ),在点燃最后一只大鼠 7 天后再注射一次 PTZ。然后将大鼠分为两组:急性注射 VPA(400 毫克/千克)或静脉注射生理盐水。通过高压液相色谱法(HPLC)评估了大鼠前额叶皮层、海马、杏仁核和纹状体中氨基酸、犬尿酸(KYNA)、单胺及其代谢物的浓度:结果发现,在PTZ诱导的大鼠中,单次给药VPA可增加前额叶皮层、海马、杏仁核和纹状体中的γ-氨基丁酸(GABA)、色氨酸(TRP)、5-羟基吲哚乙酸(5-HIAA)和KYNA浓度,降低天冬氨酸(ASP)水平:我们的研究结果表明,给 PTZ 致伤大鼠注射一次 VPA 可恢复兴奋性神经递质(降低天门冬氨酸水平)和抑制性神经递质(增加 GABA 和 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血清素能神经递质。
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来源期刊
Pharmacological Reports
Pharmacological Reports 医学-药学
CiteScore
8.40
自引率
0.00%
发文量
91
审稿时长
6 months
期刊介绍: Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures. Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology. Studies of plant extracts are not suitable for Pharmacological Reports.
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