Effects of valproate on leukocyte phagocytosis in mice and in a rat model of depression
| Authors | |
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| Year of publication | 2004 |
| Type | Article in Periodical |
| Magazine / Source | European Neuropsychopharmacology |
| MU Faculty or unit | |
| Citation | |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | depression; valproate; rat; olfactory bulbectomy; immunity; leukocyte phagocytosis |
| Description | Study with sodium valproate (VAL) was performed in mice and in a rat model of depression measuring drug effect on leukocyte phagocytosis, one of the cell immune functions. The differential white cell count was also analysed as there are controversial reports regarding the VAL effect on the number of leukocyte cells. One-hour chemiluminometric curve (measurement every 5th minute) analysis of leukocyte zymosan induced luminol aided phagocytic activity was performed in vitro (blood samples were collected from the retro-orbital plexus under a short ether anaesthesia) after repeated administration of VAL in vivo. In mice VAL doses of 37.5, 75, and 150 mg/kg/day were administered orally for 5 days. In both, sham-operated and OB rats VAL was administered orally at the dose of 75 mg/kg/day for 14 days. The leukocyte phagocytosis in VAL treated groups of naive mice and sham-operated rats was significantly (p<0.05) below the control values. However, these findings were inconsistent in mice with insignificantly increased total leukocyte count after the two highest VAL doses (75 and 150 mg/kg/day for 5 days) in comparison with the data of the control group. In OB rats the leukocyte phagocytosis was strongly decreased compared with the sham-operated group. The same dose, which suppressed the leukocyte phagocytic activity in the control group, exhibited a positive influence on the impaired leukocyte phagocytosis in the OB rats serving as model of depression. Attenuation or normalization of the OB related changes by chronic (but not acute) antidepressant treatment are interpreted as antidepressant-like effects (Kelly et al., 1997).There was no statistically significant difference in the total leukocyte count in rats between sham-operated and OB groups. The present immune data acquired from the OB rat model are in agreement with accepted antidepressant activity of valproate. Results of both these experiments, however, indicate that VAL itself may cause an immunosupressive effect on physiological leukocyte phagocytosis. |
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