Repetitive fluoxetine treatment affects long-term memories but not learning

Estibaliz Ampuero, Jimmy Stehberg, Daniela Gonzalez, Nicolas Besser, Monica Ferrero, Gabriela Diaz-Veliz, Ursula Wyneken, Francisco Javier Rubio

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Fluoxetine is currently being administered for long-term maintenance and for prophylactic reasons following the remission of depressive symptoms and several other psychiatric and neurological conditions. We have previously found that in naïve adult male rats, repetitive administration of fluoxetine induced maturation of telencephalic dendritic spines. This finding was associated with the presence of a higher proportion of GluA2- and GluN2A-containing glutamate receptors. To gain further insight into the possible consequences of such synaptic re-organization on learning and memory processes, we evaluated hippocampal- and non-hippocampal-dependent memories following administration of 0.7 mg/kg fluoxetine for four weeks. Standard behavioral tasks were used: the Morris Water Maze (MWM) and Object Location Memory (OLM) tasks to assess spatial memory and the Novel Object Recognition (NOR) task to assess recognition memory. We found that treated rats showed normal learning and short-term memory (1 h post-learning). However, either recent (24 h) or remote (17 days) memories were impaired depending upon the task. Interestingly, spatial memory impairment spontaneously reverted after 6 weeks of fluoxetine withdrawal.

Original languageEnglish
Pages (from-to)92-100
Number of pages9
JournalBehavioural Brain Research
Publication statusPublished - 5 Jun 2013


  • Antidepressants
  • Cortex
  • Explicit memory
  • Hippocampus

ASJC Scopus subject areas

  • Behavioral Neuroscience


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