Laboratory of Psychopharmacology, Institute of Drugs and Medicines Research, Federal University of Paraíba, Brazil.
Laboratory of Psychopharmacology, Institute of Drugs and Medicines Research, Federal University of Paraíba, Brazil.
Neurochem Int. 2024 Nov;180:105841. doi: 10.1016/j.neuint.2024.105841. Epub 2024 Aug 28.
Pentylenetetrazole (PTZ), a tetrazole derivative, is commonly used as a chemical agent to induce neurological disorders and replicate the characteristics of human epileptic seizures in animal models. This review offers a comprehensive analysis of the behavioral, neurophysiological, and neurochemical changes induced by PTZ. The epileptogenic and neurotoxic mechanisms of PTZ are associated with an imbalance between the GABAergic and glutamatergic systems. At doses exceeding 60 mg/kg, PTZ exerts its epileptic effects by non-competitively antagonizing GABA receptors and activating NMDA receptors, resulting in an increased influx of cations such as Na and Ca. Additionally, PTZ promotes oxidative stress, microglial activation, and the synthesis of pro-inflammatory mediators, all of which are features characteristic of glutamatergic excitotoxicity. These mechanisms ultimately lead to epileptic seizures and neuronal cell death, which depend on the dosage and method of administration. The behavioral, electroencephalographic, and histological changes associated with PTZ further establish it as a valuable preclinical model for the study of epileptic seizures, owing to its simplicity, cost-effectiveness, and reproducibility.
戊四氮（PTZ）是一种四唑衍生物，常被用作化学诱导剂，以在动物模型中诱发神经紊乱并复制人类癫痫发作的特征。本综述全面分析了 PTZ 诱导的行为、神经生理和神经化学变化。PTZ 的致痫和神经毒性机制与 GABA 能和谷氨酸能系统之间的失衡有关。在超过 60mg/kg 的剂量下，PTZ 通过非竞争性拮抗 GABA 受体和激活 NMDA 受体发挥其致痫作用，导致阳离子（如 Na 和 Ca）的流入增加。此外，PTZ 还会促进氧化应激、小胶质细胞激活和促炎介质的合成，这些都是谷氨酸能兴奋毒性的特征。这些机制最终导致癫痫发作和神经元细胞死亡，其取决于剂量和给药方式。PTZ 引起的行为、脑电图和组织学变化进一步确立了它作为癫痫发作研究的有价值的临床前模型，这归因于其简单、经济有效和可重复性。
