Exenatide Treatment Exerts Anxiolytic- and Antidepressant-Like Effects and Reverses Neuropathy in a Mouse Model of Type-2 Diabetes
Ipek Komsuoglu Celikyurt, Oguz Mutlu, Guner Ulak, Emre Uyar, Emine Bektaş, Furuzan Yildiz Akar, Faruk Erden, Ilhan Tarkun
Department of Medical Pharmacology, Psychopharmacology Lab, Medical Faculty, Kocaeli University, Kocaeli, Turkey
Med Sci Monit Basic Res 2014; 20:112-117
Comorbid neurobehavioral disturbances and type-2 diabetes mellitus (T2DM) warrant immediate research attention. Exenatide, which is a potent and selective agonist for the glucagon-like peptide-1 (GLP-1), is used in the treatment of T2DM. Exenatide displays a multitude of effects in the central nervous system. The aim of this study was to investigate the anxiolytic- and antidepressant-like effects and analgesic effects of exenatide in a type-2 diabetic mouse model.
Material and Methods: Modified elevated plus-maze test for anxiolytic-like, forced swimming test for depression-like behavior and hotplate test for neuropathy were used as behavioral tasks. Behavioral parameters were investigated in a streptozocin – (100 mg/kg, i.p.) and nicotinamide – (240 mg/kg, i.p.) induced type-2 diabetic mouse model. Exenatide (0.1 µg/kg, s.c., twice daily) was administered for 2 weeks. Vehicle (control), diabetic, and exenatide-treated diabetic mice were tested.
Results: Our results confirm that exenatide exerts anxiolytic- and antidepressant-like effects and might be effective in diabetic neuropathy in a diabetic mouse model.
Conclusions: Exenatide may be a good candidate as a treatment option for depression, anxiety, and neuropathy in patients with type-2 diabetes.
Keywords: Antidepressive Agents - therapeutic use, Anti-Anxiety Agents - therapeutic use, Animals, Diabetes Mellitus, Experimental - physiopathology, Diabetes Mellitus, Type 2 - physiopathology, Diabetic Neuropathies - physiopathology, Disease Models, Animal, Immobilization, Maze Learning - drug effects, Mice, Inbred BALB C, Motor Activity - drug effects, Peptides - therapeutic use, Reaction Time - drug effects, Time Factors, Venoms - therapeutic use