Kindling epileptogenesis in immature rats leads to persistent depressive behavior

Andréy Mazarati

Don Shin

Stéphane Auvin

Rochelle Caplan

Raman Sankar

^{Department of Pediatrics, David Geffen School of Medicine at UCLA}

^{Department of Neurology, David Geffen School of Medicine at UCLA}

^{Pediatric Neurology Department, Lille University Hospital, Lille, Cedex, France}

^{Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA}

Corresponding author: Andrey Mazarati, MD, PhD, David Geffen School of Medicine at UCLA Room 22-474 MDCC (175217) Los Angeles, CA 90095-1752 E-mail: ude.alcu@itarazam Phone: 310-206-5198 Fax: 310-825-5834

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Abstract

Depression is a frequent comorbidity in epilepsy patients. A variety of biological factors may underlie epilepsy-associated depression. We examined whether kindling-induced chronic increase in seizure susceptibility is accompanied by behavioral symptoms of depression. Three week-old Wistar rats underwent rapid kindling - 84 initially subconvulsant electrical stimulations of ventral hippocampus delivered every five minutes - followed by depression-specific behavioral tests performed two and four weeks later. Kindled animals exhibited sustained increase in the immobility time in the forced swim test and the loss of taste preference towards calorie-free saccharin, as compared to controls. Initial loss of preference towards the intake of calorie-containing sucrose was followed by the increased consumption at four weeks. At both time points, animals exhibited enhanced seizure susceptibility upon test stimulations of the hippocampus. We conclude that neuronal plastic changes associated with kindling state are accompanied by the development of depressive behavior.

Keywords: Epilepsy, depression, kindling, forced swim test, taste preference, rat

Abstract

Footnotes

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