Cytoskeleton of hippocampal neurons as a target for valproic acid in an experimental model of depression.
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 (I.P.) 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.
Instituto de Investigaciones Farmacológicas (ININFA-UBA/CONICET), (1113) Buenos Aires, Argentina.
Alejandro J
AJ
Ferrero
Marina
M
Cereseto
Laura L
LL
Sifonios
Analía
A
Reinés
Estanislao
E
Peixoto
Modesto C
MC
Rubio
Silvia
S
Wikinski
D000818:Animals; D000928:Antidepressive Agents; D001284:Atrophy; D001522:Behavior, Animal / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications / Q000523:psychology; D013550:Swimming / Q000523:psychology; D016707:Tissue Fixation; D014635:Valproic Acid / Q000494:pharmacology*
D000928:Antidepressive Agents; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D014635:Valproic Acid