Amiri Shayan, Haj-Mirzaian Arya, Amini-Khoei Hossein, Razmi Ali, Shirzadian Armin, Rahimi-Balaei Maryam, Olson Carl O, Mohsenzadeh Arman, Rastegar Mojgan, Zarrindast Mohammad-Reza, Ghazi-Khansari Mahmoud
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box, 13145-784, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Biochemistry & Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box, 13145-784, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Eur J Pharmacol. 2017 Feb 15;797:106-114. doi: 10.1016/j.ejphar.2017.01.024. Epub 2017 Jan 21.
Adolescence is a pivotal period of brain development during lifespan, which is sensitive to stress exposure. Early social isolation stress (SIS) is known to provoke a variety of psychiatric comorbidities as well as seizure risk. Psychiatric comorbidities present challenging dilemmas for treatment and management in people with seizure disorders. In this study, we aimed to investigate whether gabapentin (GBP) as an anti-epileptic drug is able to alleviate the seizure activity as well as comorbid behavioral abnormalities in socially isolated mice. Results showed that early SIS induced proconvulsant effects along with depressive, aggressive and anxiety-like behaviors. Whereas the administration of both acute and chronic GBP at sub-effective doses produced no alterations in the behavioral profile of socially conditioned counterparts the same treatments effectively reversed the seizure susceptibility to pentylenetetrazole and behavioral deficits in isolated mice. Results of the study indicate that 1) Early SIS could be considered as an animal model of psychosocial stress to investigate the psychiatric comorbidities in seizure disorders, 2) Chronic administration of low dose GBP prevented the shaping of behavioral abnormalities in adulthood, 3) Chronic administration of low dose GBP produced no negative behavioral effects in socially conditioned mice suggesting the safety of the drug, 4) Gabapentin at low doses may be considered as an agent for management of epilepsy in individuals with psychiatric comorbidities.
青春期是一生中大脑发育的关键时期，这一时期对压力暴露敏感。早期社会隔离应激（SIS）已知会引发多种精神疾病共病以及癫痫发作风险。精神疾病共病给癫痫患者的治疗和管理带来了具有挑战性的难题。在本研究中，我们旨在调查作为抗癫痫药物的加巴喷丁（GBP）是否能够减轻社会隔离小鼠的癫痫活动以及共病行为异常。结果表明，早期SIS会诱导惊厥前效应以及抑郁、攻击和焦虑样行为。而以亚有效剂量急性和慢性给予GBP对社会条件对照小鼠的行为特征没有产生改变，但相同的处理有效地逆转了隔离小鼠对戊四氮的癫痫易感性和行为缺陷。研究结果表明：1）早期SIS可被视为一种心理社会应激动物模型，用于研究癫痫疾病中的精神疾病共病；2）慢性给予低剂量GBP可防止成年期行为异常的形成；3）慢性给予低剂量GBP对社会条件小鼠没有产生负面行为影响，表明该药物的安全性；4）低剂量加巴喷丁可被视为治疗伴有精神疾病共病的个体癫痫的一种药物。
