Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA241

Poster Communications

Agomelatine prevents streptozotocin-induced diabetes and ameliorates diabetic encephalopathy in mice

H. Kelestimur1, M. Ozcan2, O. Bulmus1, N. Ulker1, I. Serhatlioglu2, E. Kacar1, A. Ayar3

1. Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey. 2. Department of Biophysics, Faculty of Medicine, Firat University, Elazig, Turkey. 3. Department of Physiology, Faculty of Medicine, Karadeniz Technical University, Elazig, Turkey.


Antidepressants are first-line treatments of neuropathic pain. Agomelatine is an antidepressant with a novel mode of action, acting as an MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist. Agomelatine has been shown to exert a clear-cut antihypersensitivity effect in streptozocin (STZ) - induced diabetic neuropathy model. The present study investigated the efficacy of agomelatine in the prevention of diabetes itself and treatment of diabetic encephalopathy with a focus on oxidative stress and inflammatory processes in the brains of streptozotocin (STZ)-induced diabetic mice. Diabetes was induced in mice by intraperitoneal (i.p.) injection of STZ. In the acute experiment, agomelatine was given i.p. 45 minutes before STZ injection. In the chronic experiment, agomelatine treatment was performed six weeks after STZ injection, and following confirmation of development of diabetes, agomelatine was given. Interleukine-1β (IL-1β) and TACR1 (NK1), which is a tachykinine receptor, were used for the investigation of inflammation in the brain regions including raphe nuclues, periaqueduqtal gyrus (PAG), amygdala and nucleus accumbens by using real-time polymerase chain reaction (RT-PCR). Agomelatine treatment prevented both hyperglycemia and hypoinsulinemia in STZ-treated mice in a dose-dependent manner. There were no significant changes in plasma triglycerides, total cholesterol and HDL-C levels of diabetic rats treated with agomelatine (5, 10 and 20 mg/kg). However, there was a significant reduction in the LDL-C level in all treated diabetic rats compared to the diabetic control group. Both acute and chronic agomelatine treatments caused changes in IL-1b mRNA and TACR1 mRNA levels in raphe nuclues PAG, amygdala and nucleus accumbens of diabetic mice. Agomelatine increased total antioxidant capacity. In conclusion, our findings suggest agomelatine seems to both prevent development of diabetes and reverse the encephalopathic changes caused by diabetes.

Where applicable, experiments conform with Society ethical requirements