Cytoskeleton of hippocampal neurons as a target for valproic acid in an experimental model of depression

Alejandro J. Ferrero, Marina Cereseto, Laura L. Sifonios, Analía Reinés, Estanislao Peixoto, Modesto C. Rubio, Silvia Wikinski

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background: Atrophy of pyramidal hippocampal neurons and of the entire hippocampus has been reported in experimental models of depression and in depressive patients respectively. We investigated the efficacy of valproic acid (VPA) for reversing a depressive-like behaviour and a cytoskeletal alteration in the hippocampus, the loss of the light neurofilament subunit (NF-L). Methods: Depressive-like behaviour was induced by inescapable stress. Animals were divided into four groups: two to assess the response to 21 days of treatment with 200 mg/kg (IP) of valproic acid, and two in which the treatment was interrupted and the effects of VPA were evaluated 90 days later. Depressive-like behaviour was evaluated by the quantification of escape movements in a swimming test. NF-L was quantified by immunohistochemistry in dentate gyrus and CA3 of hippocampus. Results: VPA corrected the depressive-like behaviour and reversed the diminution of NF-L in the hippocampus. Ninety days after the end of the treatment, and in contrast to the results previously obtained with fluoxetine, no recurrence of the depressive-like behaviour was observed. Conclusions: Despite interruption of the treatment, a long-lasting effect of VPA was observed. A possible relationship between the effect on NF-L and the prevention of depressive-like behaviour recurrence could be suggested.

Original languageEnglish (US)
Pages (from-to)1419-1428
Number of pages10
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Issue number7
StatePublished - Oct 1 2007
Externally publishedYes

Bibliographical note

Funding Information:
We wish to thank Dr. A. Serra for his advice in the preliminary discussion of our results. This work was supported by grants from Universidad de Buenos Aires (UBACYT M-013), ANPyCT-PICT 05-11102 (Argentina) and PIP5870 (CONICET).


  • Hippocampal atrophy
  • Learned helplessness
  • Mood stabilizers
  • Neurofilaments
  • Recurrent depression


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