Antidepressant suppression of non-REM sleep spindles and REM sleep impairs hippocampus-dependent learning while...

Rapid eye movement (REM) sleep enhances hippocampus-dependent associative memory, but REM deprivation has little impact on striatum-dependent procedural learning. Antidepressant medications are known to inhibit REM sleep, but it is not well understood if antidepressant treatments impact learning and memory. We explored antidepressant REM suppression effects on learning by training animals daily on a spatial task under familiar and novel conditions, followed by training on a procedural memory task. Daily treatment with the antidepressant and norepinephrine reuptake inhibitor desipramine (DMI) strongly suppressed REM sleep in rats for several hours, as has been described in humans. We also found that DMI treatment reduced the spindle-rich transition-to-REM sleep state (TR), which has not been previously reported. DMI REM suppression gradually weakened performance on a once familiar hippocampus-dependent maze (reconsolidation error). DMI also impaired learning of the novel maze (consolidation error). Unexpectedly, learning of novel reward positions and memory of familiar positions were equally and oppositely correlated with amounts of TR sleep. Conversely, DMI treatment enhanced performance on a separate striatum-dependent, procedural T-maze task that was positively correlated with the amounts of slow-wave sleep (SWS). Our results suggest that learning strategy switches in patients taking REM sleep-suppressing antidepressants might serve to offset sleep-dependent hippocampal impairments to partially preserve performance. State-performance correlations support a model wherein reconsolidation of hippocampus-dependent familiar memories occurs during REM sleep, novel information is incorporated and consolidated during TR, and dorsal striatum-dependent procedural learning is augmented during SWS.