title: Effect of acute and chronic tianeptine on the action of classical antiepileptics in the mouse maximal electroshock model.
abstract: BACKGROUND
  The aim of the study was to analyze the influence of acute and chronic treatment with tianeptine, an antidepressant selectively accelerating presynaptic serotonin reuptake, on the protective activity of classical antiepileptic drugs in the maximal electroshock test in mice.
  
  
  METHODS
  Electroconvulsions were produced by means of an alternating current (50 Hz, 25 mA, 0.2 s) delivered via ear-clip electrodes. Motor impairment and long-term memory deficits in animals were quantified in the chimney test and in the passive-avoidance task, respectively. Brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay.
  
  
  RESULTS
  Acute and chronic treatment with tianeptine (25-50 mg/kg) did not affect the electroconvulsive threshold. Furthermore, tianeptine applied in both acute and chronic protocols enhanced the anticonvulsant action of valproate and carbamazepine, but not that of phenytoin. Neither acute nor chronic tianeptine changed the brain concentrations of valproate, carbamazepine or phenytoin. On the other hand, both single and chronic administration of tianeptine diminished the brain concentration of phenobarbital. In spite of this pharmacokinetic interaction, the antidepressant enhanced the antielectroshock action of phenobarbital. In terms of adverse effects, acute/chronic tianeptine (50 mg/kg) and its combinations with classic antiepileptic drugs did not impair motor performance or long-term memory in mice.
  
  
  CONCLUSIONS
  The obtained results justify the conclusion that tianeptine may be beneficial in the treatment of depressive disorders in the course of epilepsy.
authors.affiliation: Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University, Jaczewskiego 8, PL-20-954 Lublin, Poland. kinga.borowicz@umlub.pl
authors.forename: Kinga K
authors.initials: KK
authors.lastname: Borowicz
authors.forename: Monika
authors.initials: M
authors.lastname: Banach
authors.forename: Barbara
authors.initials: B
authors.lastname: Piskorska
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy*; D005454:Fluorescence Polarization; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D013841:Thiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D013841:Thiazepines; C050504:tianeptine