title: Effects of fluoxetine on the anticonvulsant action of valproate and ethosuximide in mouse model of myoclonic convulsions.
abstract: Depression is becoming a growing problem in rural areas. This psychiatric disorder often accompanies epilepsy. The aim of this study was to assess the influence of fluoxetine (FXT), a commonly used antidepressant, on the protective action of two conventional antiepileptic drugs: ethosuximide (ETX) and valproate (VPA), against pentylenetetrazole (PTZ)-induced convulsions in mice. Motor coordination and long-term memory deficits induced by FXT, antiepileptic drugs alone and in combinations with FXT were assessed in the chimney test and passive-avoidance task, respectively. Brain concentrations of ETX and VPA were measured by immunofluorescence. Obtained results indicate that FXT at the dose of 15 mg/kg (i.p., 30 min before the test) significantly increased the threshold for clonic convulsions. The antidepressant drug at lower doses remained ineffective in this respect. Moreover, FXT at the highest subprotective dose (10 mg/kg, i.p.) markedly enhanced the anticonvulsant effects of VPA, but not of ETX, against PTZ-induced seizures. The interaction between FXT and VPA seems to be pharmacodynamic because the antidepressant drug did not alter the brain concentration of VPA. With regard to adverse effects, FXT, VPA, ETX, and the combinations of FXT with antiepileptic drugs, did not impair motor coordination and long-term memory in mice. In conclusion, the combination of FXT with VPA may be advantageous in the treatment of myoclonic epilepsy, and therefore it should be recommended for further study in clinical conditions.
authors.affiliation: Experimental Neuropathophysiology Unit, Department of Pathophysiology, Medical University, Lublin, Poland. kinga.borowicz@umlub.pl
authors.forename: Kinga K
authors.initials: KK
authors.lastname: Borowicz
authors.forename: Barbara
authors.initials: B
authors.lastname: Piskorska
authors.forename: Barbara
authors.initials: B
authors.lastname: Stępniak
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001362:Avoidance Learning; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004831:Epilepsies, Myoclonic / Q000139:chemically induced / Q000188:drug therapy*; D005013:Ethosuximide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005455:Fluorescent Antibody Technique; D005473:Fluoxetine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D057567:Memory, Long-Term; D051379:Mice; D009043:Motor Activity; D010433:Pentylenetetrazole / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014635:Valproic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D003292:Convulsants; D005013:Ethosuximide; D005473:Fluoxetine; D010433:Pentylenetetrazole; D017367:Selective Serotonin Reuptake Inhibitors; D014635:Valproic Acid