TY - JOUR
T1 - Chronic agomelatine treatment corrects the anormalities in the circadian rhythm of motor activity andb sleep/wake cycle induced by prenatal restraint stress in adult rats
AU - Mairesse, Jerome
AU - Silletti, Viviana
AU - Laloux, Charlotte
AU - Zuena, Anna Rita
AU - Giovine, Angela
AU - Consolazione, Michol
AU - Van Camp, Gilles
AU - Malagodi, Marithe
AU - Gaetani, Silvana
AU - Cianci, Silvia
AU - Catalani, Assia
AU - Mennuni, Gioacchino
AU - Mazzetta, Alessandro
AU - Van Reeth, Olivier
AU - Gabriel, Cecilia
AU - Mocaër, Elisabeth
AU - Nicoletti, Ferdinando
AU - Morley-Fletcher, Sara
AU - MacCari, Stefania
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
KW - Agomelatine
KW - hippocampus
KW - motor activity
KW - prenatal restraint stress
KW - sleep
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U2 - 10.1017/S1461145711001970
DO - 10.1017/S1461145711001970
M3 - Article
C2 - 22310059
AN - SCOPUS:84875915508
VL - 16
SP - 323
EP - 338
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
SN - 1461-1457
IS - 2
ER -