title: REM sleep homeostasis in the absence of REM sleep: Effects of antidepressants.
abstract: Most antidepressants suppress rapid eye movement (REM) sleep, which is thought to be important to brain function, yet the resulting REM sleep restriction is well tolerated. This study investigated the impact of antidepressants with different mechanisms of action, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCA), on the regulation of REM sleep in rats. REM sleep was first demonstrated to be homeostatically regulated using 5, 8 and 10 h of REM-sleep specific restriction through EEG-triggered arousals, with an average of 91 ± 10% of lost REM sleep recovered following a 26-29 -hour recovery period. Acute treatment with the antidepressants paroxetine, citalopram and imipramine inhibited REM sleep by 84 ± 8, 84 ± 8 and 69 ± 9% respectively relative to vehicle control. The pharmacologically-induced REM sleep deficits by paroxetine and citalopram were not fully recovered, whereas, after imipramine the REM sleep deficit was fully compensated. Given the marked difference between REM sleep recovery following the administration of paroxetine, citalopram, imipramine and REM sleep restriction, the homeostatic response was further examined by pairing REM sleep specific restriction with the three antidepressants. Surprisingly, the physiologically-induced REM sleep deficits incurred prior to suppression of REM sleep by all antidepressants was consistently recovered. The data indicate that REM sleep homeostasis remains operative following subsequent treatment with antidepressants and is unaffected by additional pharmacological inhibition of REM sleep.
authors.affiliation: Lilly Research Laboratories, Windlesham, Surrey, GU20 6PH, UK; Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guilford, Surrey, GU2 7XP, UK. Electronic address: a.mccarthy@surrey.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: McCarthy
authors.affiliation: Lilly Research Laboratories, Windlesham, Surrey, GU20 6PH, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Wafford
authors.affiliation: Lilly Research Laboratories, Windlesham, Surrey, GU20 6PH, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Shanks
authors.affiliation: Lilly Research Laboratories, Windlesham, Surrey, GU20 6PH, UK.
authors.forename: Marcin
authors.initials: M
authors.lastname: Ligocki
authors.affiliation: Lilly Research Laboratories, Windlesham, Surrey, GU20 6PH, UK.
authors.forename: Dale M
authors.initials: DM
authors.lastname: Edgar
authors.affiliation: Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guilford, Surrey, GU2 7XP, UK.
authors.forename: Derk-Jan
authors.initials: DJ
authors.lastname: Dijk
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Paradoxical sleep; Recovery; Selective serotonin reuptake inhibitors; Sleep deprivation; Tricyclic antidepressants