Surgical and pharmacological suppression of glucocorticoids prevents the enhancement of morphine conditioned place preference by uncontrollable stress in rats

Rationale Stress and one of the physiological components of most stress responses, glucocorticoid hormones (CORT), are known to influence the rewarding effects of a number of drugs of abuse. We have previously shown that an acute uncontrollable stressor (inescapable shock, IS) potentiates the rewarding effects of morphine using conditioned place preference (CPP).Objectives The following experiments were conducted to determine the role of CORT in this process.Methods First, the CORT response to 3.0 mg/kg morphine was measured in male Sprague–Dawley rats 24 h following exposure to IS. Second, we determined the effect of adrenalectomy (ADX) on the IS-potentiated CPP to morphine. Finally, we used the temporary CORT synthesis inhibitors metyrapone and aminoglutethimide to determine the necessity of CORT rises during either IS or morphine administration on the potentiated CPP response.Results Prior IS significantly potentiated the CORT response to morphine. ADX significantly blocked the potentiated CPP to morphine produced by previous IS. However, CORT inhibition during IS had no effect on the IS potentiation of morphine CPP, whereas inhibition during morphine administration completely blocked this potentiation.Conclusions The results indicate that the CORT response to morphine is enhanced in rats that were previously exposed to an uncontrollable stressor, and that this response to the drug, not the stressor, is necessary for the stress-enhanced potentiation of morphine CPP.     

知柏地黄丸对肾上腺皮质激素型肾阴虚幼龄大鼠血浆CORT、ACTH、CRH及肾上腺指数和组织学结构的影响

目的:探讨知柏地黄丸对肾阴虚幼龄大鼠血CORT、ACTH、CRH及肾上腺指数和肾上腺组织学结构的影响。方法:用氢化可的松每日腹腔注射法造成肾阴虚模型。结果:与空白组比较,模型组cAMP含量无变化,cGMP含量明显降低,cAMP/cGMP含量明显升高,说明造模成功。与模型组比较,知柏地黄丸高剂量组可明显提高血浆CORT、ACTH、CRH及肾上腺指数。其疗效明显优于六味地黄丸组。知柏地黄丸低剂量组与六味地黄丸组比较,治疗效果无显著差异。镜下观察可见,模型组肾上腺各层明显变薄,皮质层萎缩尤为明显,部分细胞退行性变,类脂质空泡减少。知柏地黄丸治疗后,肾上腺各层增厚,退行性变细胞明显减少,类脂质空泡较多。结论:知柏地黄丸能显著提高激素性肾阴虚幼龄大鼠血浆CORT、ACTH、CRH及肾上腺指数,故证实该药可有效拮抗外源性糖皮质激素对HPA轴的抑制作用。     

电针百会、印堂对慢性应激模型大鼠体重及HPA轴影响的研究

目的:探讨电针对慢性应激抑郁模型大鼠体重及HPA轴相关激素的影响。方法:将40只雄性SD大鼠随机分为正常对照组、抑郁模型组、电针治疗组和百优解组,每组10只。采用放射免疫分析法测定大鼠下丘脑CRF,垂体ACTH,肾上腺、血清CORT。含量。结果:抑郁模型组动物下丘脑CRF,肾上腺、血清CORT含量较正常组有显著升高;电针治疗和百优解均可使抑郁模型组动物下丘脑CRF,肾上腺、血清CORT含量显著下降。结论:电针可明显改善慢性应激模型大鼠HPA轴相关激素,对慢性应激模型大鼠体重有良性调整作用。     

右归丸对肾阳虚模型大鼠下丘脑-垂体-肾上腺轴的影响

目的:探讨右归丸对肾阳虚模型大鼠下丘脑-垂体-肾上腺轴的影响。方法:将60只健康雄性SD大鼠随机分为右归丸组、模型组和空白组,每组20只。右归丸组大鼠接受肾阳虚模型制备后予右归丸灌胃给药干预;模型组大鼠接受肾阳虚模型制备后接受右归丸组同体积的0.9%NaCl灌胃,连续灌胃20 d;空白组大鼠不接受造模制备,第16日起同右归丸组同体积的0.9%Nacl灌胃,连续灌胃20日。造模结束后每隔4日常规记录大鼠体质量、肛温、饮水量、尿量、以及抓取激惹反应。比较3组大鼠促肾上腺皮质激素释放因子(CRF)、促肾上腺皮质激素(ACTH)、大鼠皮质醇(CORT)、促肾上腺皮质激素释放激素受体1(CRHR1)的含量变化。结果:1)造模后发现接受模型制备的大鼠表现为肛温降低,饮水量及摄食量减少,体质量下降,大便溏薄,尿量增多,抓取激惹反应减弱。进行药物干预后,右归丸组大鼠的肛温、饮水量、摄食量、抓取激惹反应、体质量均高于模型组比较,差异有统计学意义(P0.05),尿量减少,且大便干湿趋于正常;2)与空白组比较模型组及右归丸组肾上腺、下丘脑、垂体的脏器指数均下降(P0.05),其中模型组下降的趋势更为明显,右归丸组较模型组肾上腺、下丘脑、垂体的脏器指数有所上升(P0.05);3)与空白组比较,模型组及右归丸组大鼠接受造模后血清CRF、ACTH、CORT以及肾上腺、下丘脑、垂体的CRHR1含量均明显下降,经过右归丸干预后,该组别的大鼠CRF、ACTH、CORT、CRHR1含量均得到提升,其中CRF、ACTH含量接近空白组水平。4)与空白组比较,模型组及右归丸组大鼠接受造模后肾上腺、下丘脑、垂体的CRF、ACTH、CORT及CRHR1 mRNA水平均明显下降,经过右归丸干预后,该组别的大鼠CRF、ACTH、CORT、CRHR1mRNA水平均得到提升。结论:右归丸可能是通过调节下丘脑-垂体-肾上腺皮质轴的功能发挥温肾补阳的作用。     

调神疏肝针法治疗抑郁症的临床疗效观察

[目的]观察调神疏肝针法治疗抑郁症的临床疗效，并探讨其对抑郁症患者神经内分泌的作用。[方法]将110例抑郁症患者随机分为调神疏肝针法组、传统针刺组和西药对照组，分别治疗6周，在治疗前后测定汉密尔顿抑郁量表(HRSD)、抑郁自评量表(SDS)，并用放免法测定促肾上腺皮质激素(ACTH)、皮质醇(CORT)的含量。[结果]调神疏肝针法可改善抑郁症患者的临床症状，调节功能亢进的下丘脑一垂体一肾上腺轴(HPA轴)，起到抗抑郁的作用。[结论]调神疏肝针法可望作为一种新的治疗抑郁症的方法。     

Electroconvulsive therapy,depression, the immune system and inflammation: A systematic review

Background

The management and treatment of major depressive disorder are major public health challenges, the lifetime prevalence of this illness being 4.4%–20% in the general population. Major depressive disorder and treatment resistant depression appear to be, in part, related to a dysfunction of the immune response. Among the treatments for depression ECT occupies an important place. The underlying cerebral mechanisms of ECT remain unclear.

多因素诱导建立慢性疲劳综合征动物模型的实验研究

目的：采用多因素诱导的造模方法建立慢性疲劳大鼠动物模型。方法：采用束缚＋游泳＋昼夜颠倒＋空瓶刺激等4种应激方法建立慢性疲劳大鼠模型。并通过M水迷宫实验、力竭游泳实验、旷场实验、糖水消耗实验等行为学指标以及血清CORT、ACTH等实验室检测指标,与双因素造模方法（束缚＋游泳）进行比较。结果：实验研究发现,多因素致慢性疲劳模型大鼠一般状态的改变、各行为学实验得分以及血清CORT、ACTH含量与双因素模型大鼠比较均有明显差异。多因素致慢性疲劳模型大鼠体力疲劳程度较双因素组加重;学习记忆能力减退更为明显;情绪变化更加复杂多样,而非单纯抑郁;血清CORT、ACTH含量更高。结论：多因素应激方法建立的慢性疲劳大鼠模型,其行为学的改变更接近人的CFS的临床表现,可以作为CFS研究的动物模型。     

左归丸和右归丸对皮质酮所致大鼠海马神经细胞病理模型学习记忆相关信号转导蛋白表达的影响

目的:观察左归丸和右归丸含药鼠血清对皮质酮所致大鼠海马神经细胞病理模型学习记忆相关信号转导蛋白表达的影响。方法:体外采用高浓度皮质酮(10-4M)处理细胞制作皮质酮损伤型大鼠海马病理细胞模型。采用Westernblot和免疫细胞化学法观察模型细胞与学习记忆相关的信号转导蛋白表达变化及左归丸和右归丸含药鼠血清的干预作用。结果:与空白对照组比较,皮质酮模型组细胞与学习记忆相关的信号转导分子pCaMKII、pCREB、pERK、pCREB和Arc蛋白表达、以及相关受体蛋白GR、MR、TrkB、NR1的表达均明显降低(P<0.05);与皮质酮模型组比较,含10%浓度的左归丸和右归丸鼠血清对模型细胞上述各项指标的异常变化均有显著改善作用(P<0.05)。结论:补肾方药—左归丸和右归丸能够改善高浓度皮质酮所致的海马神经细胞内学习记忆相关信号转导蛋白的异常表达。     

Nutraceuticals to promote neuronal plasticity in response to corticosterone-induced stress in human neuroblastoma cells

Objectives: To search for novel compounds that will protect neuronal cells under stressed conditions that may help to restore neuronal plasticity.

Methods: A model of corticosterone (CORT)-induced stress in human neuroblastoma cells (SH-SY5Y) was used to compare the efficacy of 6 crude extracts and 10 pure compounds (6 polyphenols, 2 carotenoids, 1 amino acid analogue, and 1 known antidepressant drug) to increase neuronal plasticity and to decrease cytotoxicity.

Results: Astaxanthin (among pure compounds) and phlorotannin extract of Fucus vesiculosus (among crude extracts) showed a maximum increase in cell viability in the presence of excess CORT. BDNF-VI mRNA expression in SH-SY5Y cells was significantly improved by pretreatment with quercetine, astaxanthin, curcumin, fisetin, and resveratrol. Among crude extracts, xanthohumol, phlorotannin extract (Ecklonia cava), petroleum ether extract (Nannochloropsis oculata), and phlorotannin extract (F. vesiculosus) showed a significant increase in BDNF-VI mRNA expression. CREB1 mRNA expression was significantly improved by astaxanthin, β-carotene, curcumin, and fluoxetine whereas none of the crude extracts caused significant improvement. As an adjunct of fluoxetine, phlorotannin extract (F. vesiculosus), β-carotene, and xanthohumol have resulted in significant improvement in BDNF-VI mRNA expression and CREB1 mRNA expression was significantly improved by phlorotannin extract (F. vesiculosus). Significant improvement in mature BDNF protein expression by phlorotannin extract (F. vesiculosus) and β-carotene as an adjunct of fluoxetine confirm their potential to promote neuronal plasticity against CORT-induced stress.

Discussion: The carotenoids, flavonoids, namely quercetine, curcumin, and low molecular weight phlorotannin-enriched extract of F. vesiculosus may serve as potential neuroprotective agents promoting neuronal plasticity in vitro.

Graphical abstract: Cascade of events associated with disturbed homeostatic balance of glucocorticoids and impact of phlorotannin extract (F. vesiculosus) and β-carotene in restoring neuronal plasticity. Abbreviation: TrKB, tropomyosin receptor kinase B; P-ERK, phosphorylated extracellular signal-related kinase; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; Ca++/CaMK, calcium/calmodulin-dependent protein kinase; pCREB, phosphorylated cAMP response element-binding protein; CRE, cAMP response elements, CORT, corticosterone; and BDNF; brain-derived neurotrophic factor.     

The effects of hormones and physical exercise on hippocampal structural plasticity

The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration.