The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Int J Mol Sci. 2018 Aug 20;19(8):2461. doi: 10.3390/ijms19082461.


Researches that are related to the central nervous system complications of diabetes have indicated higher incidence of cognitive disorders in patients. Since the variety of nootropic drugs used in clinics is limited and none of them consistently improves the outcomes, new and effective drug alternatives are needed for the treatment of diabetes-induced cognitive disorders. Based on the nootropic potential of agomelatine, the promising efficacy of this drug on cognitive impairments of diabetic rats was investigated in the current study. Experimental diabetes model was induced by streptozotocin. After development of diabetes-related cognitive impairments in rats, agomelatine (40 and 80 mg/kg) was administrated orally for two weeks. Cognitive performance was assessed by Morris water-maze and passive avoidance tests. Then, the total numbers of neurons in both dentate gyrus and Cornu Ammonis (CA) 1⁻3 subfields of the hippocampus were estimated by the optical fractionator method. Agomelatine treatment induced notable enhancement in the learning and memory performance of diabetic rats. Moreover, it reversed the neuronal loss in the hippocampal subregions of diabetic animals. Obtained results suggest that agomelatine has a significant potential for the treatment of diabetes-induced cognitive impairments. However, therapeutic efficacy of this drug in diabetic patients suffering from cognitive dysfunctions needs to be confirmed by further clinical trials.

Keywords: diabetes mellitus; hippocampus; learning; memory; optic fractionator.

MeSH terms

  • Acetamides / therapeutic use*
  • Animals
  • Cell Count
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / pathology
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / etiology
  • Diabetes Complications / pathology
  • Diabetes Mellitus, Experimental / complications*
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Neurons / drug effects
  • Neurons / pathology
  • Nootropic Agents / therapeutic use*
  • Rats, Sprague-Dawley


  • Acetamides
  • Nootropic Agents
  • agomelatine