Chronic agomelatine treatment corrects the abnormalities in the circadian rhythm of motor activity and sleep/wake cycle induced by prenatal restraint stress in adult rats.
Agomelatine is a novel antidepressant acting as an MT1/MT2 melatonin receptor agonist/5-HT2C serotonin receptor antagonist. Because of its peculiar pharmacological profile, this drug caters the potential to correct the abnormalities of circadian rhythms associated with mood disorders, including abnormalities of the sleep/wake cycle. Here, we examined the effect of chronic agomelatine treatment on sleep architecture and circadian rhythms of motor activity using the rat model of prenatal restraint stress (PRS) as a putative 'aetiological' model of depression. PRS was delivered to the mothers during the last 10 d of pregnancy. The adult progeny ('PRS rats') showed a reduced duration of slow wave sleep, an increased duration of rapid eye movement (REM) sleep, an increased number of REM sleep events and an increase in motor activity before the beginning of the dark phase of the light/dark cycle. In addition, adult PRS rats showed an increased expression of the transcript of the primary response gene, c-Fos, in the hippocampus just prior to the beginning of the dark phase. All these changes were reversed by a chronic oral treatment with agomelatine (2000 ppm in the diet). The effect of agomelatine on sleep was largely attenuated by treatment with the MT1/MT2 melatonin receptor antagonist, S22153, which caused PRS-like sleep disturbances on its own. These data provide the first evidence that agomelatine corrects sleep architecture and restores circadian homeostasis in a preclinical model of depression and supports the value of agomelatine as a novel antidepressant that resynchronizes circadian rhythms under pathological conditions.
Neuroplasticity Team UMR 8576 CNRS 'Structural and Functional Glycobiology Unit', University Lille North of France, Villeneuve d'Ascq, France.
Jerome
J
Mairesse
Viviana
V
Silletti
Charlotte
C
Laloux
Anna Rita
AR
Zuena
Angela
A
Giovine
Michol
M
Consolazione
Gilles
G
van Camp
Marithe
M
Malagodi
Silvana
S
Gaetani
Silvia
S
Cianci
Assia
A
Catalani
Gioacchino
G
Mennuni
Alessandro
A
Mazzetta
Olivier
O
van Reeth
Cecilia
C
Gabriel
Elisabeth
E
Mocaër
Ferdinando
F
Nicoletti
Sara
S
Morley-Fletcher
Stefania
S
Maccari
D000081:Acetamides / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001143:Arousal / Q000187:drug effects; D001345:Autoradiography; D021081:Chronobiology Disorders / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors; D012149:Restraint, Physical / Q000009:adverse effects; D012893:Sleep Wake Disorders / Q000188:drug therapy* / Q000209:etiology; D013876:Thiophenes / Q000494:pharmacology; D009281:Naphthalenes
D000081:Acetamides; D006993:Hypnotics and Sedatives; D016760:Proto-Oncogene Proteins c-fos; D044094:Receptors, Melatonin; D013876:Thiophenes; C120267:S 22153; C084711:agomelatine; D009281:Naphthalenes