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

Jerome Mairesse, Viviana Silletti, Charlotte Laloux, Anna Rita Zuena, Angela Giovine, Michol Consolazione, Gilles Van Camp, Marithe Malagodi, Silvana Gaetani, Silvia Cianci, Assia Catalani, Gioacchino Mennuni, Alessandro Mazzetta, Olivier Van Reeth, Cecilia Gabriel, Elisabeth Mocaër, Ferdinando Nicoletti, Sara Morley-Fletcher, Stefania MacCari

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)323-338
Number of pages16
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number2
DOIs
Publication statusPublished - Mar 2013

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Keywords

  • Agomelatine
  • hippocampus
  • motor activity
  • prenatal restraint stress
  • sleep

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

Mairesse, J., Silletti, V., Laloux, C., Zuena, A. R., Giovine, A., Consolazione, M., Van Camp, G., Malagodi, M., Gaetani, S., Cianci, S., Catalani, A., Mennuni, G., Mazzetta, A., Van Reeth, O., Gabriel, C., Mocaër, E., Nicoletti, F., Morley-Fletcher, S., & MacCari, S. (2013). 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. International Journal of Neuropsychopharmacology, 16(2), 323-338. https://doi.org/10.1017/S1461145711001970