Fluoxetine-induced anxiety and nervousness.
The aim of this study was to model fluoxetine-induced increase in anxiety appearing in the initial phase of the treatment with this antidepressant drug. The effects of acute administration of fluoxetine given alone and co-administered with a subthreshold dose of pentetrazole (PTZ), a proconvulsant agent with well recognized anxiogenic properties, were examined in the open field test of neophobia in rats. It was found that a single injection of fluoxetine at the dose of 5 and 10 mg/kg did not change motor and exploratory behavior of rats. Furthermore, fluoxetine (10.0 mg/kg) co-administered with a subthreshold dose of PTZ (10.0 mg/kg) had a strong and selective inhibitory influence on rat exploratory behavior. Pharmacokinetic study did not show any changes in brain concentration of PTZ in fluoxetine-pretreated animals. The central mechanism of the reported effects might involve stimulation of 5-HT2C receptors by fluoxetine in animals with PTZ-induced decrease in the threshold for emotional arousal. The present data describe a new animal model to study the central action of antidepressants reflecting dysphoric-like effects observed in the initial phase of the treatment.
Zienowicz
Małgorzata
M
Department of Experimental and Clinical Pharmacology, Medical University, Krakowskie Przedmieście 26/28, PL 00-927 Warszawa, Poland. gzienow@yahoo.it
Wisłowska-Stanek
Aleksandra
A
Lehner
Małgorzata
M
Taracha
Ewa
E
Maciejak
Piotr
P
Sobolewska
Alicja
A
Szyndler
Janusz
J
Turzyńska
Danuta
D
Walkowiak
Jerzy
J
Płaźnik
Adam
A
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D005473:Fluoxetine; D010433:Pentylenetetrazole