Effects of fluoxetine on the anticonvulsant action of valproate and ethosuximide in mouse model of myoclonic convulsions

• Published in: Annals of Agricultural and Environmental Medicine Vol. 19; no. 3; pp. 487 - 490
• Main Authors: Borowicz, Kinga K, Piskorska, Barbara, Stępniak, Barbara, Czuczwar, Stanisław J
• Format: Journal Article
• Language: English
• Published: Poland Institute of Rural Health 2012
• Subjects: Animals; Anticonvulsants; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Anticonvulsants - pharmacokinetics; Antidepressants; Antidepressive Agents, Second-Generation - administration & dosage; Antidepressive Agents, Second-Generation - adverse effects; Antidepressive Agents, Second-Generation - pharmacokinetics; Antiepileptic agents; Avoidance Learning; Convulsants - toxicity; Convulsions; Convulsions & seizures; Disease Models, Animal; Dose-Response Relationship, Drug; Drug dosages; Drug Interactions; Drug Therapy, Combination; Epilepsies, Myoclonic - chemically induced; Epilepsies, Myoclonic - drug therapy; Epilepsy; Ethosuximide - administration & dosage; Ethosuximide - adverse effects; Ethosuximide - pharmacokinetics; Fluorescent Antibody Technique; Fluoxetine; Fluoxetine - administration & dosage; Fluoxetine - adverse effects; Fluoxetine - pharmacokinetics; Immunofluorescence; Long term memory; Male; Memory, Long-Term; Mental depression; Mice; Motor ability; Motor Activity; Pentylenetetrazole; Pentylenetetrazole - toxicity; Pharmacodynamics; Rural areas; Seizures; Seizures - chemically induced; Seizures - drug therapy; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - pharmacokinetics; Valproic acid; Valproic Acid - administration & dosage; Valproic Acid - adverse effects; Valproic Acid - pharmacokinetics
• ISSN: 1232-1966; 1898-2263

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.