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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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
StatePublished - 5 Jun 2013

Bibliographical note

Funding Information:
The authors thank Nataly Quezada for taking care of the animals. Funding for this study was provided by grants to U.W. from Conicyt ( Anillo ACT09_2006 ) and by Universidad de los Andes ( MED-001-09 ) to F.J.R.


  • Antidepressants
  • Cortex
  • Explicit memory
  • Hippocampus


Dive into the research topics of 'Repetitive fluoxetine treatment affects long-term memories but not learning'. Together they form a unique fingerprint.

Cite this