Kindling epileptogenesis in immature rats leads to persistent depressive behavior

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 5 minutes, followed by depression-specific behavioral tests performed 2 and 4 weeks later. Kindled animals exhibited a sustained increase in immobility time in the forced swim test and the loss of taste preference toward calorie-free saccharin, as compared with controls. Initial loss of preference toward the intake of calorie-containing sucrose was followed by the increased consumption at 4 weeks. At both time points, animals exhibited enhanced seizure susceptibility on test stimulations of the hippocampus. We conclude that neuronal plastic changes associated with the kindling state are accompanied by the development of depressive behavior.

[1]  D. Riva,et al.  Intrathecal methotrexate affects cognitive function in children with medulloblastoma , 2002, Neurology.

[2]  A. Zangen,et al.  Association between depressive behavior and absence of serotonin–dopamine interaction in the nucleus accumbens , 2001, Psychopharmacology.

[3]  C. Stafstrom,et al.  Models of epilepsy in the developing and adult brain: Implications for neuroprotection , 2005, Epilepsy & Behavior.

[4]  F. Gilliam,et al.  Relationship between depression and intractability of seizures , 2003, Epilepsy & Behavior.

[5]  F. Gilliam,et al.  Depression in Epilepsy: Ignoring Clinical Expression of Neuronal Network Dysfunction? , 2004, Epilepsia.

[6]  P. Jobe Common pathogenic mechanisms between depression and epilepsy: an experimental perspective , 2003, Epilepsy & Behavior.

[7]  D. Overstreet,et al.  The Flinders Sensitive Line rat: A selectively bred putative animal model of depression , 2005, Neuroscience & Biobehavioral Reviews.

[8]  K. Yagi,et al.  Epilepsy in the Elderly , 2000, Epilepsia.

[9]  P A Sargent,et al.  Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635 , 2004, Molecular Psychiatry.

[10]  R. Samanin,et al.  Role of serotonin and catecholamines in brain in the feeding suppressant effect of fluoxetine , 1992, Neuropharmacology.

[11]  J. Perlin,et al.  Kindling with rapidly recurring hippocampal seizures , 1985, Brain Research.

[12]  H. Michelson,et al.  An ontogenetic study of kindling using rapidly recurring hippocampal seizures. , 1991, Brain research. Developmental brain research.

[13]  R. Murison,et al.  Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions , 2005, Physiology & Behavior.

[14]  M. Canevini,et al.  Depression and Anxiety in Patients with Epilepsy , 2001, Epilepsy & Behavior.

[15]  Jingyi Ma,et al.  Schizophrenia-like behavioral changes after partial hippocampal kindling , 2004, Brain Research.

[16]  J. Moreau Validation d'un modèle animal de l'anhédonie, symptôme majeur de la dépression , 1997 .

[17]  R. Porsolt,et al.  Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity. , 1979, European journal of pharmacology.

[18]  R. Sankar Initial treatment of epilepsy with antiepileptic drugs , 2004, Neurology.

[19]  R. Murison,et al.  Chronic mild stress affects sucrose intake and sleep in rats , 2004, Behavioural Brain Research.

[20]  C. Harden The co-morbidity of depression and epilepsy: Epidemiology, etiology, and treatment , 2002, Neurology.

[21]  E. Bertram,et al.  Depression in Intractable Partial Epilepsy Varies by Laterality of Focus and Surgery , 2003, Epilepsia.

[22]  P. Willner,et al.  The validity of animal models of predisposition to depression. , 2002, Behavioural pharmacology.

[23]  C. Halldin,et al.  Limbic reductions of 5-HT1A receptor binding in human temporal lobe epilepsy , 2004, Neurology.

[24]  L. Heisler,et al.  Fluoxetine Decreases Fat and Protein Intakes But Not Carbohydrate Intake in Male Rats , 1997, Pharmacology Biochemistry and Behavior.

[25]  M. Sabatino,et al.  Effects of desipramine and alprazolam in the forced swim test in rats after long-lasting termination of chronic exposure to picrotoxin and pentylenetetrazol , 1993, European Neuropsychopharmacology.

[26]  E. Li,et al.  Effects of repeated administration of serotonergic agonists on diet selection and body weight in rats , 1991, Pharmacology Biochemistry and Behavior.

[27]  R. Sankar,et al.  Regulation of Kindling Epileptogenesis by Hippocampal Galanin Type 1 and Type 2 Receptors: The Effects of Subtype-Selective Agonists and the Role of G-Protein-Mediated Signaling , 2006, Journal of Pharmacology and Experimental Therapeutics.

[28]  F. Gonzalez-Lima,et al.  Brain systems underlying susceptibility to helplessness and depression. , 2003, Behavioral and cognitive neuroscience reviews.

[29]  R. Sankar,et al.  Age‐dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling , 2007, Epilepsia.

[30]  Gary L. Dunbar,et al.  Spatial learning deficits and emotional impairments in pentylenetetrazole-kindled rats , 2005, Epilepsy & Behavior.

[31]  M. Kulikov,et al.  Depressive-like behavioral alterations and c-fos expression in the dopaminergic brain regions in WAG/Rij rats with genetic absence epilepsy , 2003, Behavioural Brain Research.

[32]  C. Deransart,et al.  Amygdala kindling in the rat: anxiogenic-like consequences , 1996, Neuroscience.

[33]  E. Lothman,et al.  Closely spaced recurrent hippocampal seizures elicit two types of heightened epileptogenesis: a rapidly developing, transient kindling and a slowly developing, enduring kindling , 1994, Brain Research.

[34]  Mark S. Seidenberg,et al.  Psychiatric Comorbidity in Chronic Epilepsy: Identification, Consequences, and Treatment of Major Depression , 2000, Epilepsia.

[35]  D. Overstreet,et al.  Reward and anxiety in genetic animal models of childhood depression , 2005, Behavioural Brain Research.

[36]  A. Kanner Epilepsy, suicidal behaviour, and depression: do they share common pathogenic mechanisms? , 2006, The Lancet Neurology.

[37]  R. Canger,et al.  Depression and Anxiety in Patients with Epilepsy , 2001, Epilepsia.

[38]  Suresh Gurbani,et al.  Depression and Anxiety Disorders in Pediatric Epilepsy , 2005, Epilepsia.

[39]  W C Eckelman,et al.  PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy , 2003, Neurology.

[40]  L. Nyström,et al.  An incident case-referent study of epileptic seizures in adults , 1990, Epilepsy Research.

[41]  D. Guthrie,et al.  Measures of psychopathology in children with complex partial seizures and primary generalized epilepsy with absence. , 2001, Journal of the American Academy of Child and Adolescent Psychiatry.

[42]  N. Young,et al.  Kindling-induced emotional behavior in male and female rats. , 2003, Behavioral neuroscience.

[43]  A. Kanner Depression in Epilepsy: A Neurobiologic Perspective , 2005, Epilepsy currents.

[44]  M. Sabatino,et al.  NMDA-GABA interactions in an animal model of behaviour: a gating mechanism from motivation toward psychotic-like symptoms , 1994, European Neuropsychopharmacology.

[45]  Michael Seidenberg,et al.  The Relative Impact of Anxiety, Depression, and Clinical Seizure Features on Health‐related Quality of Life in Epilepsy , 2004, Epilepsia.

[46]  O. Puciłowski,et al.  Chronic mild stress-induced anhedonia: Greater effect in a genetic rat model of depression , 1993, Physiology & Behavior.