Agomelatine in the tree shrew model of depression: Effects on stress-induced nocturnal hyperthermia and hormonal status |
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| Institution: | 1. Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota;2. University of Szeged, Division of Invasive Cardiology, Second Department of Internal Medicine and Cardiology Center, Szeged, Hungary;3. Henry Ford Hospital, Detroit, Michigan;4. Columbia University, New York, New York;5. Massachusetts General Hospital, Boston, Massachusetts;6. Beth Israel Deaconess Medical Center, Boston, Massachusetts;7. VA San Diego Healthcare System and University of California San Diego, La Jolla, California;8. Baylor Heart and Vascular Hospital, Dallas, Texas;9. Medical Center of the Rockies, Loveland, Colorado;10. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;11. VA Central Arkansas Healthcare System, Little Rock, Arkansas;12. The Heart Hospital Baylor Plano, Plano, Texas;13. Torrance Memorial Medical Center, Torrance, California;14. Piedmont Heart Institute, Atlanta, Georgia;15. VA Minneapolis Healthcare System and University of Minnesota, Minneapolis, Minnesota;p. Meshalkin Siberian Federal Biomedical Research Center, Ministry of Health of Russian Federation, Novosibirsk, Russian Federation;q. Korgialeneio-Benakeio Hellenic Red Cross General Hospital of Athens, Athens, Greece;r. Emory University Hospital, Atlanta, Georgia;s. VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, Texas |
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| Abstract: | The antidepressive drug agomelatine combines the properties of an agonist of melatonergic receptors 1 and 2 with an antagonist of the 5-HT2C receptor. We analyzed the effects of agomelatine in psychosocially stressed male tree shrews, an established preclinical model of depression. Tree shrews experienced daily social stress for a period of 5 weeks and were concomitantly treated with different drugs daily for 4 weeks. The effects of agomelatine (40 mg/kg/day) were compared with those of the agonist melatonin (40 mg/kg/day), the inverse 5-HT2C antagonist S32006 (10 mg/kg/day), and the SSRI fluoxetine (15 mg/kg/day). Nocturnal core body temperature (CBT) was recorded by telemetry, and urinary norepinephrine and cortisol concentrations were measured.Chronic social stress induced nocturnal hyperthermia. Agomelatine normalized the CBT in the fourth week of the treatment (T4), whereas the other drugs did not significantly counteract the stress-induced hyperthermia. Agomelatine also reversed the stress-induced reduction in locomotor activity. Norepinephrine concentration was elevated by the stress indicating sympathetic hyperactivity, and was normalized in the stressed animals treated with agomelatine or fluoxetine but not in those treated with melatonin or S32006. Cortisol concentration was elevated by stress but returned to basal levels by T4 in all animals, irrespective of the treatment.These observations show that agomelatine has positive effects to counteract stress-induced physiological processes and to restore the normal rhythm of nocturnal CBT. The data underpin the antidepressant properties of agomelatine and are consistent with a distinctive profile compared to its constituent pharmacological components and other conventional agents. |
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| Keywords: | Melatonin Fluoxetine S32006 Norepinephrine Cortisol Telemetry |
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