title: Protective effects of gabapentin against the seizure susceptibility and comorbid behavioral abnormalities in the early socially isolated mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Shayan
authors.initials: S
authors.lastname: Amiri
authors.affiliation: 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.
authors.forename: Arya
authors.initials: A
authors.lastname: Haj-Mirzaian
authors.affiliation: Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran; Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Amini-Khoei
authors.affiliation: Department of Pharmacology and Applied Medicine, Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Razmi
authors.affiliation: 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.
authors.forename: Armin
authors.initials: A
authors.lastname: Shirzadian
authors.affiliation: Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahimi-Balaei
authors.affiliation: Department of Biochemistry & Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Carl O
authors.initials: CO
authors.lastname: Olson
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box, 13145-784, Tehran, Iran.
authors.forename: Arman
authors.initials: A
authors.lastname: Mohsenzadeh
authors.affiliation: Department of Biochemistry & Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Rastegar
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box, 13145-784, Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
authors.affiliation: 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. Electronic address: ghazikha@sina.tums.ac.ir.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghazi-Khansari
mesh_terms: D000374:Aggression / Q000187:drug effects; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001007:Anxiety / Q000150:complications; D001522:Behavior, Animal / Q000187:drug effects*; D015897:Comorbidity; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D000077206:Gabapentin; D006798:Housing; D008124:Locomotion / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D012640:Seizures / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology*; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000150:complications; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
keywords: Adolescence; Gabapentin; Psychiatric comorbidity; Seizure; Social isolation stress