Chronic treatment with fluoxetine decreases seizure threshold in naïve but not in rats exposed to the learned helplessness paradigm: Correlation with the hippocampal glutamate release

The proconvulsive effect of the new generation of antidepressants remains controversial. The authors investigated in naïve rats the effect of chronic treatment with fluoxetine (FLX) on the convulsive threshold and on two parameters of the hippocampal glutamatergic neurotransmission: the in vitro glu...

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Bibliographic Details
Published in:Progress in neuro-psychopharmacology & biological psychiatry 2005-06, Vol.29 (5), p.678-686
Main Authors: Ferrero, Alejandro J., Cereseto, Marina, Reinés, Analía, Bonavita, Carla D., Sifonios, Laura L., Rubio, Modesto C., Wikinski, Silvia I.
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents, Second-Generation - pharmacology
Behavior, Animal - drug effects
Chronic treatment
Convulsants
Dizocilpine Maleate - metabolism
Dizocilpine Maleate - pharmacology
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists - metabolism
Excitatory Amino Acid Antagonists - pharmacology
Fluoxetine
Fluoxetine - pharmacology
Glutamate release
Glutamic Acid - metabolism
Helplessness, Learned
Hippocampus
Hippocampus - drug effects
Hippocampus - metabolism
In Vitro Techniques
Learned helplessness
Male
Pentylenetetrazole
Rats
Rats, Wistar
Receptors, N-Methyl-D-Aspartate - drug effects
Receptors, N-Methyl-D-Aspartate - metabolism
Seizure threshold
Seizures - physiopathology
Synaptic Transmission - drug effects
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Summary:The proconvulsive effect of the new generation of antidepressants remains controversial. The authors investigated in naïve rats the effect of chronic treatment with fluoxetine (FLX) on the convulsive threshold and on two parameters of the hippocampal glutamatergic neurotransmission: the in vitro glutamate release and the binding of [ 3H] MK801 to NMDA receptors. While the acute treatment with FLX provoked no change either in seizure susceptibility or in the glutamate release, the chronic treatment decreased the convulsive threshold in coincidence with an increment in the in vitro glutamate release. No significant effects on the binding of [ 3H] MK801 to NMDA receptors were found to be attributable to the FLX treatment. We also assessed the effect of the chronic treatment with FLX on the seizure threshold in rats exposed to an experimental model of depression, the learned helplessness paradigm (LH). While a decrease in the K +-stimulated glutamate release was observed in non treated LH animals, when they were chronically injected with FLX, no changes in the epileptic susceptibility and no increments in the glutamate release were found. Our results indicate that chronic treatment with FLX decreases the epileptic threshold in naïve but not in LH rats and that this effect correlates with the levels of the hippocampal glutamate release.
ISSN:0278-5846
1878-4216
DOI:10.1016/j.pnpbp.2005.04.013