Fluoxetine and the dentate gyrus: memory, recovery of function, and electrophysiology.
Chronic fluoxetine increases neurogenesis in the dentate gyrus (DG). In view of the widespread clinical use of fluoxetine and the well-established role of the DG in memory, surprisingly few studies have examined the effects of fluoxetine on memory and hippocampal electrophysiology. Additionally, few studies have evaluated the potential for fluoxetine to promote recovery of function after DG damage. Therefore, we studied the effects of long-term administration of fluoxetine on both spatial-reference memory and working memory, recovery of function after intrahippocampal colchicine infusions, which can destroy 50-70% of DG granule cells, and electrophysiological responses in the DG to perforant path stimulation in freely moving rats. Chronic fluoxetine did not affect matching-to-place or reference-memory performance in intact rats in the Morris water-maze task. Surprisingly, in rats with DG damage, recovery of function on both tasks was adversely affected by chronic fluoxetine. Finally, unlike an earlier study that reported fluoxetine-induced increases in hippocampal population spike amplitudes and excitatory postsynaptic potential slopes in urethane-anesthetized rats, electrophysiological measures in DG of freely moving rats were not affected by chronic fluoxetine treatment.
Keith
Julian R
JR
Department of Psychology, University of North Carolina at Wilmington, North Carolina 28403-5612, USA. keithj@uncw.edu
Wu
Ying
Y
Epp
Jonathon R
JR
Sutherland
Robert J
RJ
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000494:pharmacology*; D003078:Colchicine / Q000633:toxicity; D018891:Dentate Gyrus; D004334:Drug Administration Schedule; D004594:Electrophysiology; D005473:Fluoxetine / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced; D051381:Rats; D020318:Rats, Long-Evans; D013028:Space Perception / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D003078:Colchicine