Repetitive fluoxetine treatment affects long-term memories but not learning

• Published in: Behavioural brain research Vol. 247; pp. 92 - 100
• Main Authors: Ampuero, Estibaliz, Stehberg, Jimmy, Gonzalez, Daniela, Besser, Nicolas, Ferrero, Monica, Diaz-Veliz, Gabriela, Wyneken, Ursula, Rubio, Francisco Javier
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.06.2013; Elsevier
• Subjects: Animals; Antidepressants; Behavioral psychophysiology; Biological and medical sciences; Cortex; Explicit memory; Fluoxetine - pharmacology; Fundamental and applied biological sciences. Psychology; Hippocampus; Hippocampus - drug effects; Male; Maze Learning - drug effects; Medical sciences; Memory, Long-Term - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopharmacology; Rats; Rats, Sprague-Dawley; Recognition (Psychology) - drug effects; Serotonin Uptake Inhibitors - pharmacology; Space Perception - drug effects; Explicit memory; Antidepressants; Hippocampus; Cortex; Serotonin; Fluoxetine; Psychotropic; Central nervous system; Long-term memory; Reuptake inhibitor; Encephalon; Selective serotonin reuptake inhibitor; Learning; Acquisition process; Treatment; Neurotransmitter; Antidepressant agent
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2013.03.011

•Fluoxetine treatment specifically impairs long-term memory.•Fluoxetine treatment does not affect learning.•Fluoxetine withdrawal restores impairment in spatial memory, but not in recognition memory. 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 0.7mg/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 (1h post-learning). However, either recent (24h) or remote (17 days) memories were impaired depending upon the task. Interestingly, spatial memory impairment spontaneously reverted after 6 weeks of fluoxetine withdrawal.