title: Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC.
abstract: BACKGROUND
  Agomelatine is described as a novel and clinical effective antidepressant drug with melatonergic (MT(1)/MT(2)) agonist and 5-HT(2C) receptor antagonist properties. Previous studies suggest that modulation of neuronal plasticity and microtubule dynamics may be involved in the treatment of depression.
  
  
  OBJECTIVE
  The present study investigated the effects of agomelatine on microtubular, synaptic and brain-derived neurotrophic factor (BDNF) proteins in selected rat brain regions.
  
  
  METHODS
  Adult male rats received agomelatine (40 mg/kg i.p.) once a day for 22 days. The pro-cognitive effect of agomelatine was tested in the novel object recognition task and antidepressant activity in the forced swimming test. Microtubule dynamics markers, microtubule-associated protein type 2 (MAP-2), phosphorylated MAP-2, synaptic markers [synaptophysin, postsynaptic density-95 (PSD-95) and spinophilin] and BDNF were measured by Western blot in the hippocampus, amygdala and prefrontal cortex (PFC).
  
  
  RESULTS
  Agomelatine exerted pro-cognitive and antidepressant activity and induced molecular changes in the brain areas examined. Agomelatine enhanced microtubule dynamics in the hippocampus and to a higher magnitude in the amygdala. By contrast, in the PFC, a decrease in microtubule dynamics was observed. Spinophilin (dendritic spines marker) was decreased, and BDNF increased in the hippocampus. Synaptophysin (presynaptic) and spinophilin were increased in the PFC and amygdala, while PSD-95 (postsynaptic marker) was increased in the amygdala, consistent with the phenomena of synaptic remodelling.
  
  
  CONCLUSIONS
  Agomelatine modulates cytoskeletal microtubule dynamics and synaptic markers. This may play a role in its pharmacological behavioural effects and may result from the melatonergic agonist and 5-HT(2C) antagonist properties of the compound.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale-UMR788, Le Kremlin-Bicêtre, France.
authors.forename: Nataly
authors.initials: N
authors.lastname: Ladurelle
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gabriel
authors.forename: Adela
authors.initials: A
authors.lastname: Viggiano
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mocaër
authors.forename: Etienne E
authors.initials: EE
authors.lastname: Baulieu
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bianchi
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D013569:Synapses / Q000378:metabolism; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C084711:agomelatine; D009281:Naphthalenes