The effects of valproate in brain monoamines of juvenile rats after stress

1. Clinical data suggest that valproate (VPA) may be useful in prophylaxis of affective disorders, which show disturbances of the serotoninergic system. On the other hand, chronic stress has an adverse effect on affective disorders, those with disturbances of the serotonergic system, especially. 2. In order to study the effects of VPA on brain monoamines and acute stress, 200 mgr VPA/Kgr was administered intraperitoneal (ip) to juvenile male rats; the control group was treated with NaCL 0.9% ip. After 30 min, all animals were evoked on predictable neurogenic or systemic stress (30 min foot shock, or 15 min ether stress, respectively), and 48 hours later, VPA or NaCL were administered ip again; 30 min afterwards, the rats were decapitated. Rats without stress were also sacrificed 30 min after VPA or NaCL administration. 3. Measurements of brain monoamines noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA), were done in Frontal Cortex (FC), Hypothalamus (HY) and Striatum (S), by High Performance Liquid Chromatography (HPLC). 4. Compared with the control stress group the level of 5-HIAA in the FC was significantly increased (P < 0.01) in VPA stress rats; in the HY and in S the increase of 5-HIAA was not significant. No remarkable differences were observed in NA, DA, 5-HT and DOPAC concentrations, in any of the brain regions. No changes in brain monoamine levels were found in non stress rats, either. 5. The augmentation of 5-HIAA level after VPA administration and after stress, in correlation with the decrease of 5-HIAA that is observed in depression, support the hypothesis that VPA may be effective in affective disorders by influencing the serotoninergic system.