Fluoxetine protects hippocampal plasticity during conditioned fear stress and prevents fear learning potentiation.
BACKGROUND
Contextual fear conditioning can produce both changes in hippocampal synaptic efficacy and potentiation of subsequent fear learning.


OBJECTIVE
In this study, we tested whether fluoxetine reverses these effects.


METHODS
In the first experiment, we examined alterations of baseline synaptic efficacy and induction of synaptic plasticity in the CA3 region of the hippocampus during re-exposure of rats, treated with fluoxetine (7 mg/kg) or vehicle, in a context where they previously received 15 eyelid shocks or no shock (controls). In the second experiment, fear learning potentiation was examined in rats that were initially submitted to conditioning (15 eyelid shocks) and extinction training and then re-exposed to a less intense stressor (three eyelid shocks).


RESULTS
Conditioned fear stress decreased synaptic efficacy and blocked the induction of synaptic potentiation in the fimbria-CA3 pathway. Conditioned rats treated with fluoxetine were protected against these electrophysiological changes and did not differ from controls (i.e., no depression and normal induction of potentiation of synaptic efficacy). However, fluoxetine treatment did not suppress conditioned freezing. After fear extinction, exposure of rats to a subconditioning stressor provoked conditioning (fear learning potentiation) in rats treated with vehicle but not in those treated with fluoxetine.


CONCLUSIONS
These findings indicate that fluoxetine treatment, which is ineffective on conditioned fear stress-induced freezing, may have beneficial effects on conditioned fear stress-induced disturbance of hippocampal plasticity. These data also suggest that restoration of hippocampal functioning may contribute to protection against exaggerated reactions to mild stressors reported in patients with post-traumatic stress disorder.
Spennato
Guillaume
G
Laboratoire de Neurobiologie et Psychopathologie, Université de Nice-Sophia Antipolis, JE2441 Nice, France.
Zerbib
Carine
C
Mondadori
Cesare
C
Garcia
René
R
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004597:Electroshock; D005143:Eyelids; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007858:Learning / Q000187:drug effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013315:Stress, Psychological / Q000503:physiopathology
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors