Possible anti-depressant effect of efavirenz and pro-depressive-like effect of voriconazole in specified doses in various experimental models of depression in mice.

BACKGROUND: Reports from experimental and clinical studies have indicated the possible relation between cholesterol and depression. Efavirenz (EFV) and Voriconazole (VRC) have been reported to affect cholesterol-24S-hydroxylase enzyme. The objective of the present study was to evaluate the effect of EFV and VRC in experimental models of depression in mice.

METHODS: There was a measurement of immobility time in forced swim test and tail suspension test in which mice were previously subjected to the treatment of EFV (0.09mg/kg, orally (po)) and VRC (75mg/kg, intraperitoneally (ip)) separately for 14days. Sucrose intake was measured during stress schedule of 21days in chronic mild stress model in which mice were subjected to above mentioned drug treatment for last 14days. There was an estimation of serum total cholesterol and brain serotonin levels on day 21.

RESULTS: The results indicated that mice treated with EFV showed a significant decrease in the immobility time and increase in sucrose intake with decrease in serum total cholesterol. Mice treated with VRC showed a significant increase in the immobility time and decrease in the sucrose intake with increase in serum total cholesterol. There was a significant increase and decrease in brain serotonin levels in mice treated with EFV and VRC respectively.

CONCLUSION: The results of the present study indicates the possible anti-depressant effect of EFV and pro-depressive-like effect of VRC in specified doses in mice, raising the possibility that stimulation but not inhibition of cholesterol-24S-hydroxylase may be important in the treatment of depression.