Spike-wave discharges are necessary for the expression of behavioral depression-like symptoms

Epilepsia. 2010 Jan;51(1):146-60. doi: 10.1111/j.1528-1167.2009.02260.x. Epub 2009 Aug 8.


Purpose: The WAG/Rij strain of rats, a well-established model for absence epilepsy, has comorbidity for depression. These rats exhibit depression-like behavioral symptoms such as increased immobility in the forced swimming test and decreased sucrose intake and preference (anhedonia). These depression-like behavioral symptoms are evident in WAG/Rij rats, both at 3-4 and 5-6 months of age, with a tendency to aggravate in parallel with an increase in seizure duration. Here we investigated whether the behavioral symptoms of depression could be prevented by the suppression of absence seizures.

Methods: Ethosuximide (ETX; 300 mg/kg/day, in the drinking water) was chronically applied to WAG/Rij rats from postnatal day 21 until 5 months. Behavioral tests were done before the cessation of the treatment. Electroencephalography (EEG) recordings were made before and after cessation of treatment to measure seizure severity at serial time-points.

Results: ETX-treated WAG/Rij rats exhibited no symptoms of depression-like behavior in contrast to untreated WAG/Rij rats of the same age. Moreover, treated WAG/Rij rats did not differ from control age-matched Wistar rats. ETX treatment led to almost complete suppression of spike-wave discharges (SWDs) in 5-6 month old WAG/Rij rats. Discontinuation of chronic treatment was accompanied by a gradual emergence of SWDs; however, a persistent reduction in seizure activity was still present 47 days after discontinuation of the chronic treatment.

Discussion: The results suggest that seizure activity is necessary for the expression of depression-like behavioral symptoms and confirm that epileptogenesis can be prevented by early and chronic treatment.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Antidepressive Agents / pharmacology
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Depression / diagnosis*
  • Depression / genetics
  • Depressive Disorder / diagnosis
  • Depressive Disorder / genetics
  • Disease Models, Animal
  • Electroencephalography / drug effects
  • Electroencephalography / statistics & numerical data*
  • Epilepsy, Absence / diagnosis
  • Epilepsy, Absence / genetics*
  • Epilepsy, Absence / prevention & control
  • Ethosuximide / pharmacology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Immobility Response, Tonic / physiology
  • Male
  • Models, Genetic
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Rats
  • Rats, Inbred Strains
  • Rats, Wistar
  • Seizures / chemically induced*
  • Swimming / physiology


  • Anticonvulsants
  • Antidepressive Agents
  • Ethosuximide