title: Effects of early long-term treatment with antiepileptic drugs on development of seizures and depressive-like behavior in a rat genetic absence epilepsy model.
abstract: OBJECTIVE
  Depression is most commonly associated with epilepsy. Recent reports have suggested a putative relationship between seizure development and onset of depressive behavior, whereas others proposed that two clinical entities might represent different neuropathologic aspects of the same neurologic disorder. The WAG/Rij rat absence epilepsy model has also been proposed as a suitable model to test antidepressant drugs. We previously reported on a long-term study of two antiepileptic drugs (AEDs) to assess their protective role in absence epileptogenesis. Here, we examined the effects of long-term treatment with several AEDs on absence seizure development and onset of depressive-like behavior in WAG/Rij rats at different ages, using a forced swimming test (FST).
  
  
  METHODS
  Animals were divided into one untreated control group and four test groups, given ethosuximide, levetiracetam, zonisamide, or carbamazepine. Electroencephalography (EEG) readings were recorded at 6.5 months of age.
  
  
  RESULTS
  Ethosuximide-treated animals showed significant reductions in recorded spike-wave discharges (SWDs), and FST immobility time (IT) compared with untreated same age controls. However, zonisamide- and carbamazepine-treated animals had IT values similar to those of controls, but only zonisamide significantly decreased absence seizure development. Carbamazepine increased SWD incidence. Levetiracetam also protected against seizure development, while augmenting IT, suggesting a prodepressive effect.
  
  
  CONCLUSIONS
  Although treatment with ethosuximide, levetiracetam, or zonisamide reduced appearance of SWDs in WAG/Rij rats, this was not generally linked to a reduced onset of depressive characteristics, as assessed by FST. Therefore, expression of depressive-like behavior seems unrelated to seizure control in this model. Some possible alternative explanations for the observed data are discussed.
authors.affiliation: Department of Experimental and Clinical Medicine, School of Medicine, University of Catanzaro, Via T. Campanella 115, Catanzaro, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.forename: Francesca
authors.initials: F
authors.lastname: Scicchitano
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Fazio
authors.forename: Ida
authors.initials: I
authors.lastname: Perrotta
authors.forename: Ida
authors.initials: I
authors.lastname: Perrota
authors.forename: Eugenio D
authors.initials: ED
authors.lastname: Di Paola
authors.forename: Andrew
authors.initials: A
authors.lastname: Constanti
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002220:Carbamazepine / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000150:complications / Q000188:drug therapy*; D005013:Ethosuximide / Q000627:therapeutic use; D007555:Isoxazoles / Q000627:therapeutic use; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D002220:Carbamazepine; D000077287:Levetiracetam; D000078305:Zonisamide; D005013:Ethosuximide; D010889:Piracetam