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


CONCLUSIONS
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.
Sarkisova
Karine Yu
KY
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerov street 5A, Moscow 117485, Russia. karine@online.ru
Kuznetsova
Galina D
GD
Kulikov
Michael A
MA
van Luijtelaar
Gilles
G
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003863:Depression / Q000175:diagnosis* / Q000235:genetics; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data*; D004832:Epilepsy, Absence / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D005013:Ethosuximide / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D046353:Immobility Response, Tonic / Q000502:physiology; D008297:Male; D008957:Models, Genetic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*; D013550:Swimming / Q000502:physiology
D000927:Anticonvulsants; D000928:Antidepressive Agents; D005013:Ethosuximide