title: The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats.
abstract: Agomelatine, a novel antidepressant with established clinical efficacy, acts as a melatonin receptor agonist and 5-HT(2C) receptor antagonist. As stress is a significant risk factor in the development of depression, we sought to determine if chronic agomelatine treatment would block the stress-induced impairment of memory in rats trained in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. Moreover, since neural cell adhesion molecule (NCAM) is known to be critically involved in memory consolidation and synaptic plasticity, we evaluated the effects of agomelatine on NCAM, and polysialylated NCAM (PSA-NCAM) expression in rats given spatial memory training with or without predator stress. Adult male rats were pre-treated with agomelatine (10 mg/kg i.p., daily for 22 d), followed by a single day of RAWM training and memory testing. Rats were given 12 training trials and then they were placed either in their home cages (no stress) or near a cat (predator stress). Thirty minutes later the rats were given a memory test trial followed immediately by brain extraction. We found that: (1) agomelatine blocked the predator stress-induced impairment of spatial memory; (2) agomelatine-treated stressed, as well as non-stressed, rats exhibited a rapid training-induced increase in the expression of synaptic NCAM in the ventral hippocampus; and (3) agomelatine treatment blocked the water-maze training-induced decrease in PSA-NCAM levels in both stressed and non-stressed animals. This work provides novel observations which indicate that agomelatine blocks the adverse effects of stress on hippocampus-dependent memory and activates molecular mechanisms of memory storage in response to a learning experience.
authors.affiliation: Laboratory of Behavioural Genetics, Brain Mind Institute, EPFL, Lausanne, Switzerland. Lisa.Conboy@epfl.ch
authors.forename: Lisa
authors.initials: L
authors.lastname: Conboy
authors.forename: Cihan
authors.initials: C
authors.lastname: Tanrikut
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Zoladz
authors.forename: Adam M
authors.initials: AM
authors.lastname: Campbell
authors.forename: Collin R
authors.initials: CR
authors.lastname: Park
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gabriel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mocaer
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
authors.forename: David M
authors.initials: DM
authors.lastname: Diamond
mesh_terms: D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012794:Sialic Acids / Q000378:metabolism*; D013028:Space Perception / Q000187:drug effects*; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D003345:Corticosterone; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; C084711:agomelatine; D009281:Naphthalenes