Dose-dependent effects of venlafaxine on expressions of pCREB and BDNF in the rat hippocampus after chronic unpredictable stress.

Objective To explore the effects of venlafaxine on chronic unpredictable stress induced expressions of phosphorylated form of the cyclic-AMP response element binding protein(pCREB) and brain-derived neurotrophic factor(BDNF) in the rat hippocampus.Methods Sprague-Dawley rats were exposed to different chronic unpredictable stressors(CUS) for 4 weeks and were treated with venlafaxine(5 and 10 mg/kg,respectively) thereafter.All rats were divided into 8 groups with 10 rats in each group as follows: normal control(NC)、chronic unpredictable stress(MD0)、CUS+saline 14 days(MD1) and CUS+saline 28 days(MD2)、CUS+venlafaxine(5 mg/kg) 14 days(LV1) and CUS+venlafaxine(5 mg/kg) 28 days(LV2)、CUS+venlafaxine(10 mg/kg) 14 days(HV1) and CUS+venlafaxine(10 mg/kg) 28 days(HV2).The expressions of phosphorylated form of the cyclic-AMP response element binding protein(pCREB) and brain-derived neurotrophic factor(BDNF) were assessed using immunohistochemistry and Western blot.Results CUS down-regulated the expressions of pCREB and BDNF in the hippocampus of CUS rats(P0.05).Low dose of venlafaxine(5 mg/kg) treatment increased expressions of these proteins(P0.05),whereas high dose of venlafaxine(10 mg/kg) decreased expression of these proteins,but the differences between high dose treatment rats and the CUS rats were not stastically significant(P0.05).Conclusions Low dose of venlafaxine(5 mg/kg) treatment are probably associated with neuronal plasticity.The present findings suggest that neuronal plasticity-associated proteins such as pCREB and BDNF play an important role in depression.