RESUMO
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.
Assuntos
Antidepressivos , Citoesqueleto/efeitos dos fármacos , Depressão/tratamento farmacológico , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Ácido Valproico/farmacologia , Animais , Atrofia , Comportamento Animal/efeitos dos fármacos , Depressão/psicologia , Imuno-Histoquímica , Masculino , Proteínas de Neurofilamentos/metabolismo , Ratos , Ratos Wistar , Estresse Psicológico/complicações , Estresse Psicológico/psicologia , Natação/psicologia , Fixação de TecidosRESUMO
The proconvulsive effect of the new generation of antidepressants remains controversial. The authors investigated in naïve rats the effect of chronic treatment with fluoxetine (FLX) on the convulsive threshold and on two parameters of the hippocampal glutamatergic neurotransmission: the in vitro glutamate release and the binding of [3H] MK801 to NMDA receptors. While the acute treatment with FLX provoked no change either in seizure susceptibility or in the glutamate release, the chronic treatment decreased the convulsive threshold in coincidence with an increment in the in vitro glutamate release. No significant effects on the binding of [3H] MK801 to NMDA receptors were found to be attributable to the FLX treatment. We also assessed the effect of the chronic treatment with FLX on the seizure threshold in rats exposed to an experimental model of depression, the learned helplessness paradigm (LH). While a decrease in the K+-stimulated glutamate release was observed in non treated LH animals, when they were chronically injected with FLX, no changes in the epileptic susceptibility and no increments in the glutamate release were found. Our results indicate that chronic treatment with FLX decreases the epileptic threshold in naïve but not in LH rats and that this effect correlates with the levels of the hippocampal glutamate release.