title: Antidepressant action of agomelatine (S 20098) in a transgenic mouse model.
abstract: The aim of this study was to evaluate the efficacy of agomelatine (S 20098) to accelerate reversal of the neuroendocrinological, behavioural and cyclical changes seen in a transgenic mouse model of the neuroendocrine characteristics of depression. The effects of agomelatine were assessed in transgenic mice with low glucocorticoid receptor (GR) function, after acute stress or induced phase shift, and compared to desipramine and melatonin. Mice were injected 2 h before the onset of the dark period with agomelatine (10 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), melatonin (10 mg/kg, i.p.) or vehicle (hydroxy-ethyl-cellulose (HEC) 1%) each day for 21 to 42 days. Agomelatine was effective in reversing the transgenic mouse behavioural changes noted in the Porsolt forced swim test as well as in the elevated plus maze. Both the number of open arm entries and the total time spent in open arms of the elevated plus maze is greatly increased in transgenic mice. The mean time spent in open arms is exquisitely sensitive to reversal by agomelatine and desipramine. Agomelatine also markedly accelerated readjustment of circadian cycles of temperature and activity following an induced phase shift. This action of agomelatine was superior to that of melatonin while desipramine was without effect. The accelerating effect of agomelatine was particularly notable if treatment was started 3 weeks prior to the induced phase shift. Agomelatine treatment did not cause any major change in corticosterone or adrenocorticotropic hormone (ACTH) concentrations nor in vasopressin (AVP), corticotropin-releasing hormone (CRH), GR and mineralocorticoid receptor (MR) mRNAs levels, which make it unlikely that the mechanism of agomelatine action is related to hypothalamic-pituitary-adrenocortical (HPA) axis changes. The present study shows that agomelatine displays some characteristics of antidepressant drug action in the transgenic mouse model, effects that could be partially related to its chronobiotic properties.
authors: Neuroscience, CHUL Research Centre, 2705 Laurier Boulevard, Ste-Foy, Québec, Canada G1V 4G2. barden@crchul.ulaval.ca
authors: Nicholas
authors: N
authors: Barden
authors: Eric
authors: E
authors: Shink
authors: Michel
authors: M
authors: Labbé
authors: Raphaël
authors: R
authors: Vacher
authors: Joseph
authors: J
authors: Rochford
authors: Elisabeth
authors: E
authors: Mocaër
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001522:Behavior, Animal; D003345:Corticosterone / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000235:genetics; D003891:Desipramine / Q000627:therapeutic use; D004195:Disease Models, Animal; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013550:Swimming; D013686:Telemetry / Q000379:methods; D013997:Time Factors; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000324:Adrenocorticotropic Hormone; D000928:Antidepressive Agents; D003345:Corticosterone; D003891:Desipramine; D008550:Melatonin; D011965:Receptors, Glucocorticoid; C084711:agomelatine; D009281:Naphthalenes