Antidepressant action of agomelatine (S 20098) in a transgenic mouse model
| Autor: | Raphaël Vacher, Nicholas Barden, Elisabeth Mocaer, Michel Labbé, Eric Shink, Joseph Rochford |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Elevated plus maze Time Factors Chronobiotic Mice Transgenic Adrenocorticotropic hormone Pharmacology Melatonin chemistry.chemical_compound Mice Receptors Glucocorticoid Adrenocorticotropic Hormone Corticosterone Internal medicine Desipramine Acetamides medicine Agomelatine Animals Telemetry Maze Learning Biological Psychiatry In Situ Hybridization Swimming Behavior Animal business.industry Depression Antidepressive Agents Disease Models Animal Endocrinology chemistry business Behavioural despair test medicine.drug |
| Zdroj: | Progress in neuro-psychopharmacologybiological psychiatry. 29(6) |
| ISSN: | 0278-5846 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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