title: Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats.
abstract: Agomelatine is an antidepressant with a distinct pharmacological mechanism of action as an MT1 and MT2 receptor agonist and as a 5-HT2C receptor antagonist. We evaluated the chronic effects of agomelatine administration (40 mg/kg, 20 weeks) on the cognitive performance of rats in the Morris water maze task. We applied unbiased stereological quantification methods to estimate the total numbers of granular and pyramidal neurons located in the dorsal hippocampus. We also analyzed the dendritic spines of pyramidal neurons in the CA1 region using the Golgi-Cox impregnation method. The agomelatine-treated group found the hidden platform more quickly than did the control group and spent significantly more time in the target quadrant. Agomelatine administration caused significant volumetric and numerical enhancements in granular and pyramidal neurons in the dentate gyrus and CA1-3 subregions, respectively. Increased densities of the mushroom and stubby types of spines, with no alteration in the thin-shaped spines, were observed in the agomelatine-treated group. These results showed that long-term agomelatine administration induced a nootropic effect supported by structural changes. Enhancement of the more stable types of dendritic spines might indicate improved adaptive capacity in hippocampal neurons. Future studies will provide a better understanding of the effect of this drug on synaptic plasticity.
authors.affiliation: aDepartment of Pharmacology, Faculty of Pharmacy, Anadolu University bDepartment of Anatomy, Faculty of Medicine, Eskisehir Osmangazi University cInterdisciplinary Neuroscience Department, Health Science Institute of Eskişehir Osmangazi University, Eskisehir, Turkey.
authors.forename: Ümide
authors.initials: Ü
authors.lastname: Demir Özkay
authors.forename: Erdem
authors.initials: E
authors.lastname: Söztutar
authors.forename: Özgür Devrim
authors.initials: ÖD
authors.lastname: Can
authors.forename: Umut İrfan
authors.initials: Uİ
authors.lastname: Üçel
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Öztürk
authors.forename: Emel
authors.initials: E
authors.lastname: Ulupinar
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D018697:Nootropic Agents; C084711:agomelatine; D009281:Naphthalenes