The effect of fluoxetine in a model of chemically induced seizures--behavioral and immunocytochemical study.
The aim of this study was to examine the effects of acute fluoxetine treatment on pentylenetetrazol-induced convulsions in order to shape a model of seizures associated with treatment with antidepressants in rats. Moreover, the putative role of the hippocampal formation in this respect was investigated with the help of c-fos immuncytochemistry to mark local neuronal activity. It was found that fluoxetine (10.0 mg/kg, i.p.) enhanced the proconvulsive effect of pentylenetetrazol (50.0 mg/kg, i.p.), and simultaneously inhibited pentylenetetrazol-stimulated c-Fos expression in some areas of the hippocampus. Fluoxetine pretreatment did not alter pentylenetetrazol brain concentration indicating that this phenomenon was not related to the pharmacokinetic interaction. It is suggested that inhibition by fluoxetine of some neuronal populations contributing to the local feedback mechanism controlling excessive epileptiform discharges within the hippocampus might lead to an increase in epileptic activity. The reported in the present paper fluoxetine versus pentylenetetrazol interaction may, therefore, serve as a model of seizures associated with treatment with antidepressants.
Zienowicz
Małgorzata
M
Department of Experimental and Clinical Pharmacology, Warsaw Medical University, 26/28 Krakowskie Przedmiescie Street, 00-927 Warsaw, Poland.
Wisłowska
Aleksandra
A
Lehner
Małgorzata
M
Taracha
Ewa
E
Skórzewska
Anna
A
Maciejak
Piotr
P
Płaźnik
Adam
A
D000818:Animals; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D005473:Fluoxetine / Q000627:therapeutic use / Q000633:toxicity*; D006624:Hippocampus / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control
D005473:Fluoxetine; D010433:Pentylenetetrazole