Jahan Kausar, Pillai Krishna K, Vohora Divya
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
Fundam Clin Pharmacol. 2017 Aug;31(4):403-410. doi: 10.1111/fcp.12283. Epub 2017 Apr 26.
The present study was designed to investigate the role of serotonin and other neurotransmitters namely dopamine (DA), histamine, nor-epinephrine (NE), glutamate, and γ-aminobutyric acid (GABA) in the 6-Hz-induced psychomotor seizures in Swiss albino mice. Parachlorophenylalanine (PCPA, 300 mg/kg/day, i.p for 3 days)-treated mice were given 6-Hz stimulation. Sodium valproate (SVP) (200 mg/kg/day, p.o for 3 days) was used as a reference antiepileptic drug. The behavioral changes induced by 6 Hz including increased rearing and grooming, Straub's tail, behavioral arrest, stun position were amplified by PCPA. The 6-Hz-induced seizures were accompanied by reduced brain 5-HT, DA, NE, histamine, GABA, and enhanced glutamate levels. PCPA facilitated further reduction of endogenous 5-HT and DA levels but not NE, histamine, GABA, and glutamate levels. Pre- and post-treatment with SVP protected the mice from 6-Hz seizures and attenuated PCPA-induced changes in the levels of 5-HT and DA in the mice brain suggesting the protective effect of SVP in the pharmacoresistant model of epilepsy involving mainly serotonergic mechanism. However, the study also suggests modulation of other neurotransmitters both in 6-Hz psychomotor seizures and in the action of SVP against such seizures.
本研究旨在探讨血清素及其他神经递质，即多巴胺（DA）、组胺、去甲肾上腺素（NE）、谷氨酸和γ-氨基丁酸（GABA）在6赫兹诱导的瑞士白化小鼠精神运动性癫痫发作中的作用。对用对氯苯丙氨酸（PCPA，300毫克/千克/天，腹腔注射，共3天）处理的小鼠进行6赫兹刺激。丙戊酸钠（SVP）（200毫克/千克/天，口服，共3天）用作参考抗癫痫药物。PCPA放大了6赫兹诱导的行为变化，包括竖毛和理毛增加、施特劳布尾、行为停滞、晕厥姿势。6赫兹诱导的癫痫发作伴随着脑内5-羟色胺、多巴胺、去甲肾上腺素、组胺、GABA水平降低以及谷氨酸水平升高。PCPA促使内源性5-羟色胺和多巴胺水平进一步降低，但对去甲肾上腺素、组胺、GABA和谷氨酸水平无影响。SVP预处理和后处理可保护小鼠免受6赫兹癫痫发作的影响，并减弱PCPA诱导的小鼠脑内5-羟色胺和多巴胺水平变化，提示SVP在主要涉及血清素能机制的癫痫耐药模型中具有保护作用。然而，该研究还表明，在6赫兹精神运动性癫痫发作以及SVP对抗此类癫痫发作的作用中，其他神经递质也受到了调节。
