RGD Reference Report - Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC. - Rat Genome Database

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Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC.

Authors: Ladurelle, N  Gabriel, C  Viggiano, A  Mocaer, E  Baulieu, EE  Bianchi, M 
Citation: Ladurelle N, etal., Psychopharmacology (Berl). 2012 Jun;221(3):493-509. doi: 10.1007/s00213-011-2597-5. Epub 2011 Dec 8.
RGD ID: 10043819
Pubmed: PMID:22160164   (View Abstract at PubMed)
DOI: DOI:10.1007/s00213-011-2597-5   (Journal Full-text)

RATIONALE: 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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to xenobiotic stimulus  IEP 10043819agomelatineRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppp1r9b  (protein phosphatase 1, regulatory subunit 9B)


Additional Information