title: Agomelatine restores a physiological response to stress in the aged rat.
abstract: Short duration immobilization stress (IS) in younger rats is followed by a sleep rebound involving slow wave sleep (SWS) and, more particularly, rapid eye movement (REM) sleep. This rebound, expressing the ability of the brain to confront a stress challenge, is now accepted as a marker of the homeostasis. In older rats (24-25 months), however, an IS of 1h is not followed by a sleep rebound. To determine whether this impairment is reversible, we analyzed the effects of the antidepressant agomelatine, on stress-related sleep rebound in older animals. Older and younger (3-5 months) rats were equipped with electroencephalographic (EEG) and electromyographic (EMG) electrodes and polygraphic recordings were achieved under basal conditions with a digitized set-up. Older rats were pretreated with agomelatine (40mg/kg/day) for 3 days, with IS applied on the third day, whereas younger rats were only subjected to IS. Polygraphic recordings achieved under basal conditions confirmed the conventional impairments of the sleep/wake architecture in older animals, including decreased delta power, shortened REM sleep bouts, and modified sleep/wake circadian rhythms. Older rats pretreated with agomelatine for 3 days showed a reversal of the deficit observed in the beta-1, but not in the delta, EEG power band. Application of an IS to older rats after agomelatine pretreatment resulted in a REM sleep rebound in response to stress. These findings indicate that agomelatine, by improving beta-1 EEG power band and by inducing stress-related sleep rebound in older animals, contributes to the homeostasis maintenance.
authors.affiliation: INSERM, U1028, Lyon Neuroscience Research Center, Lyon F-69008, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Descamps
authors.affiliation: INSERM, U1028, Lyon Neuroscience Research Center, Lyon F-69008, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Rousset
authors.affiliation: INSERM, U1028, Lyon Neuroscience Research Center, Lyon F-69008, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Dugua
authors.affiliation: INSERM, U1028, Lyon Neuroscience Research Center, NeuroChem Platform, Lyon F-69008, France.
authors.forename: G
authors.initials: G
authors.lastname: Debilly
authors.affiliation: Neuropsychiatry Innovation Therapeutic Pole, Institut de Recherches Servier, 125 chemin de Ronde, 78290 Croissy-sur-Seine, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.affiliation: INSERM, U1028, Lyon Neuroscience Research Center, Lyon F-69008, France. Electronic address: cespuglio@univ-lyon1.fr.
authors.forename: Raymond
authors.initials: R
authors.lastname: Cespuglio
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000375:Aging / Q000502:physiology / Q000523:psychology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004569:Electroencephalography; D007103:Immobilization; D008297:Male; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology; D014851:Wakefulness / Q000187:drug effects; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; C084711:agomelatine; D009281:Naphthalenes
keywords: Agomelatine; Immobilization stress; Rapid eye movement sleep (REM sleep); Sleep rebound; Slow wave sleep (SWS); Younger or Older rats