Effect of γ-aminobutyric acid B receptors on the expression of brain-derived neurotrophic factor in hippocampus of rats with diabetic neuropathic pain with depression

Abstract

Objective To investigate the effect γ-aminobutyric acid B (GABAB) receptors on the expression of brain-derived neurotrophic factor (BDNF) in rats with diabetic neuropathic pain (DNP) with depression by using GABAB receptors agonist (baclofen) and antagonists (CGP55845).Methods 100 male SD rats were randomly divided into two groups:normal control group (C group) and DNP with depression model group (D group),in which the rats were intraperitonealy injected with saline or streptozocin (STZ) respectively.The DNP with depression models were established in 80 rats three weeks after the forced swimming test (FST),and 80 rats were randomly divided into 4 subgroups (n =20,each group) according to the given medicines:saline 10 μl + saline 10 μl injected intrathecally in D1 group,baclofen 0.5 μg + saline 10 μl in D2 group,CGP55845 10 μg + saline 10 μl in D3 group,and CGP55845 10 μg +baclofen 0.5 μg in D4 group.Saline 10 μl + saline 10 μl were injected intrathecally in 20 normal rats (C group).There was an interval of 15 min between twice intrathecal injections in five groups for 4 days.The paw withdrawal threshold (PWT) and immobility time of FST (IMFST) were measured two h (T1) and two weeks after intrathecal injection (T2) respectively.The hippocampi of rats were removed after measurements of PWT and IMFST for detection of BDNF expression.Results As compared with C group,the PWT was significantly reduced [(13.02 ± 1.68) g vs.(3.46 ±0.84) g,P ＜0.05],the IMFST was significantly prolonged [(47.14 ±3.65) s vs.(178.12 ± 12.49) s,P ＜0.05],and the expression of BDNF was decreased (P ＜ 0.05) in D group.As compared with D1 group,the IMFST was significantly shortened (P ＜ 0.05) in D2 and D3 groups,the expression of BDNF was increased (P ＜ 0.05) in D2 and D3 groups,and the PWT was significantly increased (P ＜ 0.05) in D2 group but showed no significant change in D3 group.The PWT,IMFST and expression of BDNF showed no significant change in D4 group as compared with D1 group.The PWT,IMFST and the expression of BDNF showed no significant change between T1 and T2 in five groups.Conclusion GABAB receptors could up-regule the expression of BDNF in the hippocampi of rats with DNP with depression,and alleviate the depression symptoms. Key words: Diabetic ; Brain-derived neurotrophic factor; Pain; Depression ; γ-aminobutyric acid B receptors