Effects of ketamine on expression of hippocampal GABAB1 receptors and BDNF in rats with diabetic neuropathic pain complicated with depression

Abstract

Objective To evaluate the effects of ketamine on the expression of gamma-aminobutyric acid type B receptor subunit 1 (GABAB1) receptors and brain-derived neurotrophic factor (BDNF) in rats with diabetic neuropathic pain (DNP) complicated with depression.Methods Pathogen-free male Sprague-Dawley rats,weighing 180-200 g,were used in the study.The model of DNP was established by intraperitoneal injection of streptozocin,and then depression was induced by forcing the rats to swim in a narrow cylinder from which they cannot escape.Forty rats with DNP complicated with depression were randomly divided into 2 groups (n =20 each) using a random number table:model control group (NS group) and ketamine group (K group).In group K,ketamine 10 mg/kg (0.5 ml) was injected intramuscularly once a day for one week.In NS group,the equal volume of normal saline was given instead of ketamine.Another 20 rats were used as normal control group (C group).Mechanical paw withdrawal threshold to von Frey stimuli (MWT) was measured and the time for immobility during forced swimming test was recorded at 1 day after completion of administration (T1) and 2nd week after completion of administration (T2).After the end of behavior test,the hippocampi of rats were removed for detection of GABAB1 receptor and BDNF expression (using immunohistochemistry and Western blot) and expression of GABAB1 receptor and BDNF mRNA (using RT-PCR).Results Compared with C group,MWT was significantly decreased,the time for immobility during forced swimming test was prolonged,and the expression of GABAB1 receptor and BDNF protein and mRNA was down-regulated in group NS.Compared with group NS,MWT was significantly increased,the time for immobility during forced swimming test was shortened,and the expression of GABAB1 receptor and BDNF protein and mRNA was up-regulated in group K.Conclusion Ketamine can upregulate the expression of GABAB1 receptor and BDNF in rats with DNP complicated with depression,thus mitigating DNP and depressed state. Key words: Ketamine; Receptors, GABA-B; Brain-derived neurotrophic factor; Diabetic neuropathies ; Depression