The Role Of Monoamine Neurotransmitter And The Effect Of The Sertonin On The GR/MR And BDNF Expression Of The Hippocampus During The Stress Adaption

PARTⅠEffects of single or repeated restrain stress on themonoamines neurotransmitters in the frontal cortex, hippocampusand hypothalamus of ratsObjectives To explore the function of the monoaminesneurotransmitters in the stress adaptation by assessing the monoaminesrelease and the behavior changes in the single or repeated restrain stress.Methods 24 male Sprague-Dawley rats were randomly assigned tonormal control group, single acute stress group and repeated restrain stressgroup. 24 hours after the last restrain stress (6hour/day, ten days for therepeated stress) session, the rats were assessed by the Open Field test andthe Elevated Plus-Maze test. At last, the release of the monoaminesneurotransmitters and their metabolites in homogenates obtained from thefrontal cortex, hippocampus and hypothalamus were assessed by HPLC.Data were analyzed using one-way ANOVA followed by LSD.Results In the Open Field test, the single stress group spent less timein the center (P＜0.01), there were no significant difference between therepeated stress group and the control group in the time of spent in thecentre (P＞0.05). In the Elevated Plus-maze test, the single stress groupspent more time in the close arms, and less time in the open arms (P＜0.01),there has no significant difference between the repeated stress group andthe control group in the time spent in the close/open arms (P＞0.05). In thesingle stress group, the level of 5-HT and its metabolites 5-HIAA in thefrontal cortex and hippocampus were significantly higher than that of thecontrol (P＜0.01); the level of MHPG and NE in the frontal cortex andhypothalamus were significantly higher than that of the control (P＜0.01 orP＜0.05). In the repeated stress group, the level of 5-HT and its metabolites5-HIAA in the hippocampus was significantly higher than that of thecontrol (P＜0.01); the level of DA in the frontal cortex was significantlylower than that of the control (P＜0.01); there has no significant differenceof the catecholamines in the hippocampus between the single stress group and the control group, between the repeated group and the control group(P＞0.05).Conclusions (1) This study indicated that single stress induce theanxiety behavior of the rats, but repeat exposed the same adverse event canmake the organism adaptation to this kind of stress. (2) The single andrepeated stress can increase the release of the 5-HT in the hippocampus,which may be the critical neurobiology of the stress adaptation.PARTⅡEffects of the repeated restrain stress on the behavior,Corticosteroid Receptor immunoreactivity and BDNF mRNAexpression in the hippocampus of the 5-HT depletion ratsObjectives To explore the role of 5-HT in the stress adaptation andthe changes of corticosteroid receptor and BDNF function of thehippocampus, by using the 5-HT depletion and repeated restrain stress rats.Methods Male Sprague-Dawley rats were randomly assigned tocontrol group, repeated stress group, 5-HT depletion group and 5-HTdepletion +stress group. The p-PCA (200mg/kg, ip for two consecutivedays) was used to deplete the 5-HT, the stress model was restrain stress (6hour/days, for 10 days). After 10 days of stress, the rats were assessed bythe Open Field test, the Elevated Plus-Maze test, the Sucrose Preferencetest, the Forced Swimming test and the Morris Water Maze test. Thehippocampus corticosteroid receptor immunoireactivity and thebrain-derived neurotrophic factor (BDNF) mRNA expression wereassessed. Data were analyzed using two-way ANOVA.Results (1) Compared with the intact rats, the 5-HT depletion ratsgained significantly less weight, and showed more seriously anxiousbehavior, reduced reward sensitivity and more obvious learned helplessness according to certain behavior tests, including Open field test,Elevated plus-maze test, consumption of sucrose and Forced swimmingtest after the restrain stress. (2) Compared with the intact rats, the 5-HTdepletion rats showed significantly impaired learning and memoryaccording to Morris water maze test. (3) There was significantly increasedglucocorticoid receptor immunoreactivity in the intact rats but not in thosewith p-PCA depletion of 5-HT following the repeated stress, with thelatter showing significant BDNF mRNA downregulation.Conclusions The present study suggests that 5-HT deficiency ofthe adult rats may suppress or exacerbate hippocampal GR and BDNFfunction in the stressed animals and result in impaired adaptation to stress,further elucidating the mechanism of 5-HT system in mood and cognitiondisorders related to stress.PARTⅢEffects of postsynaptic 5-HT1A receptor function onCorticosteroid Receptor immunoreactivity and BDNF mRNAexpression in the hippocampus of the repeated restrain stress ratsObjectives Using the 5-HT1A agonist 8-OH-DPAT and antagonistWAY100635, to explore the effects of postsynaptic 5-HT1A receptors onthe GR/MR immunoreactivity and BDNF mRNA expression in thehippocampus of the 5-HT depleted rats with repeated restrain stress.Methods Male adult Sprague-Dawley rats were randomlyassigned to control group, stress group, 8-OH-DPAT group,stress+8-OH-DPAT group, WAY100635 group, stress+WAY100635group and stress+ WAY100635+8-OH-DPAT group. All rats had 5-HTdepletion by p-PCA, the 8-OH-DPAT (200mg/kg) s.c 30 min before thestress session, the WAY-100635 (300ug/kg) s.c 15 min before the stresssession, the control group used the saline (2ml/kg) s.c in the same time as the 8-OH-DPAT. The repeated restraint stress animal model was used.The hippocampus corticosteroid receptor immunoreactivity and theBDNF mRNA expression were assessed. Data were analyzed usingone-way ANOVA.Results (1) As the body weight gain, the 8-OH-DPAT group wassignificantly higher than that of control group (P＜0.01), thestress+8-OH-DPAT group was significantly higher than that of stressgroup (P＜0.01), there has no significant difference among other groups(P＞0.05). (2) Activation of post-synaptic 5-HT1A receptors by8-OH-DPAT in the 5-HT depletion rats or the 5-HT depletion stress ratscan significantly decrease the anxiety behavior in the Open Field test andthe Elevated Plus-Maze test, and reduced reward sensitivity and learnedhelplessness according to consumption of sucrose and Forced swimmingtest. This effect was prevented by the treatment with WAY100635. In theMorris Water Maze test, there has no significant difference among thegroups in the escape latency, time spent in the target quadrant and thenumber of crossing the previous place of the platform. (3) In the CA1,CA2 and CA3 of the hippocampus, the GR grey intensity level ofstress+8-OH-DPAT was significantly lower than that of group control(＜0.05). There has no significant difference among the groups in the MRgrey intensity level. In the hippocampus CA1, CA2, CA3, CA4 and DGregion, the BDNF mRNA grey intensity level of stress+8-OH-DPATgroup was significantly lower than that of the stress group (P＜0.05).Conclusions Activation of post-synaptic 5-HT1A receptors wouldattenuate the anxiety and depressive behavior, and would facilitate thehippocampus to mediate stress adaptation.