The Effect Of GABA_B Receptor Regulates Two Pore Domain Potassium Channels TREK-1 In The Pathogenesis Of Depression

Objective:SD rat model of depression was induced by chronic unpredictable stress stimulation.Through various drug interventions,the role of GABAB receptor regulates two pore domain potassium channels TREK-1 in the pathogenesis of depression was investigated.Methods:Male Sprague-Dawley(SD)rats of SPF grade,weighing 200-250g,were selected to adapt to the environment' for a week.The depression model of rats was established under chronic unpredictable stress according to the principle of random grouping.Open field test(OFT)and sucrose preference test(SPT)were used to evaluate the behavior of depression model in rats.The rats were divided into 9 groups according to different drug intervention.They were blank control group(C),depression model group(CUS),depression model GABAB agonist intervention group(CUS+Baclofen),depression model GABAB antagonist intervention group(CUS+CGP55845),depression model TREK-1 antagonist intervention group(CUS+Spadin),blank control group GABAB agonist intervention group(C+Baclofen),blank control GABAB antagonist intervention group(C+CGP55845),blank control TREK-1 antagonist intervention group(C+Spadin),positive control group(CUS+Citalopram).After drug intervention,the different changes of depression behavior were evaluated by open field test and sucrose preference test,and the expression of TREK-1 and GABAB receptors in hippocampus of rats were detected by immunohistochemistry and Western blot.To investigate the role of GABAB receptor in regulating two pore domain potassium channels TREK-1 in the pathogenesis of depression.Results:1.Compared with the normal control group,the total distance,the spent time in the central area,the crossing number,the rearing number in the CUS model group and the proportion of sugar water consumption in the sucrose preference test were significantly decreased.However,there was no significant difference in behavioral indexes of open field test and sucrose preference test between C+Baclofen group?C+CGP55845 group and C+Spadin group;Compared with CUS group,the proportion of sugar water consumption in CUS+Spadin group,CUS+CGP55845 group and CUS+Citalopram group was significantly increased.In open field test,the total distance of movement,the residence time of the central area,the horizontal score of crossing,the vertical score of rearing were significantly increased.However,compared with CUS group,the proportion of sugar water consumption,the spent time in the central area,the crossing number and the rearing number in the sucrose preference test and open field test in CUS+Baclofen group decreased obviously,and the total distance had a decreasing trend.2.The results of Western blot showed that the expression of TREK-1 channel protein and GABABreceptor protein in hippocampus of CUS group was significantly lower than that of normal control group;The expression of TREK-1 channel protein in hippocampus of CUS+Spadin group was significantly higher than that of CUS group;The expression of TREK-1 channel protein and GABABreceptor protein in hippocampus of CUS+CGP55845 group was significantly higher than that of CUS group;The expression of TREK-1 channel protein and GABAB receptor protein in hippocampus of CUS+Baclofen group was significantly lower than that of CUS group;There was no significant difference with the expression of TREK-1 channel protein and GABAB receptor protein in prefrontal cortex of rats in each group.3.The results of immunohistochemistry showed that the immunoreactivity of TREK-1 channel protein in hippocampal CA1 and CA2 region of rats in CUS group was significantly lower than that of control group;The immunoreactivity of TREK-1 channel protein in hippocampal CA1 and CA2 region of rats in CUS+Spadin group was significantly higher than that of CUS group;The immunoreactivity of TREK-1 channel protein in hippocampal CA1 and CA2 region of rats in CUS+CGP55845 group was significantly higher than that in CUS group;The immunoreactivity of TREK-1 channel protein in hippocampal CA1 and CA2 region of rats in CUS+Baclofen group was significantly lower than that of CUS groupConclusions:1.Long time chronic unpredictable stress stimulation can establish a successful depression model to simulate the formation of human depression;2.The two pore domain potassium channels TREK-1 antagonist can effectively relieve depressive symptoms in rats;3.GABAB receptor antagonist can increase the expression of TREK-1 channel in the hippocampus of rats in the depression model and alleviate the depressive symptoms in rats;4.GABAB receptor agonists can reduce the expression of TREK-1 channels in the hippocampus of rats with depression,and exacerbating depressive symptoms in rats;5.GABAB receptor regulates the two pore domain potassium channels TREK-1 in the depression.