慢性应激抑郁模型大鼠海马神经肽Y的表达及氟西汀的干预作用

目的研究慢性应激抑郁模型大鼠海马中NPY的表达情况及氟西汀的干预作用。方法将大鼠随机分为抑郁模型组、氟西汀治疗组和对照组。模型组和氟西汀组给予21 d的应激刺激,此期间对照组正常饲养,刺激期间氟西汀组每天腹腔注射氟西汀(10mg/kg),模型组和对照组每天腹腔注射等体积的生理盐水。行为学检测应用open-field法和液体消耗实验。采用western-b lotting法检测各组大鼠海马NPY表达的水平。结果应激后模型组水平穿越格数(19.5±7.2)、竖立次数(10.2±2.6)、修饰次数(6.6±2.4)、糖水消耗百分比[(53.1±9.5)%],均显著低于对照组[分别为(31.4±7.3)、(19.0±2.4)、(14.0±2.4)、(76.0±2.7);均P<0.01]。应激后氟西汀组水平穿越格数(26.2±3.5)与对照组差异无显著性(P>0.05),但高于模型组(P<0.05);竖立次数(13.9±4.2)低于对照组(P<0.01),但高于模型组(P<0.05);修饰次数(10.3±1.6)低于对照组(P<0.01),但高于模型组(P<0.01);糖水消耗百分比(61.5±8.5)%低于对照组(P<0.01),与模型组差异无显著性(P>0.05)。模型组大鼠慢性应激后海马中NPY的表达水平显著低于对照组(P<0.01));氟西汀组大鼠慢性应激后海马中NPY的表达水平显著低于对照组(P<0.01)),但明显高于模型组大鼠,差异有显著性(P<0.01)。结论慢性应激抑郁模型大鼠海马中NPY的表达降低并可以被氟西汀部分逆转。     

Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity

Rationale: Recent studies have implicated intracellular transduction pathways and neurotrophic factors in the action of antidepressants. Adaptation in these pathways may ultimately affect electrophysiological and morphological properties of neurones. We have previously shown that repeated electroconvulsive stimulation, a safe and effective antidepressant treatment, has profound effects on hippocampal synaptic connectivity and plasticity in the rat. Here, we investigated whether these electrophysiological properties were shared by the chemical antidepressant, fluoxetine. Objectives: To compare the electrophysiological and cognitive effects of two very different antidepressant treatments: repeated electroconvulsive stimulation (rECS); and chronic administration of the serotonin specific re-uptake inhibitor (SSRI), fluoxetine. Methods: Rats were exposed to either rECS or daily fluoxetine administration for 15 days. The animals were then anaesthetised and dentate field excitatory post-synaptic potential (fEPSP) characteristics were measured before and after the induction of long-term potentiation (LTP) by high frequency perforant path stimulation. In a separate experiment, the effects of rECS and chronic fluoxetine administration on acquisition and retention of a spatial learning task in the Morris watermaze were determined. Results: Chronic fluoxetine administration and rECS produced equivalent increases in dentate fEPSP compared to respective control groups. LTP induction was attenuated in both groups. Spatial learning was, in contrast, unaffected by fluoxetine treatment but significantly impaired following rECS. Conclusions: Given that fluoxetine and rECS share antidepressant properties, but differ in their effects on learning and memory, we propose that the common effects on dentate connectivity and synaptic plasticity described here are more likely to relate to affective rather than cognitive function. This result is consistent with other experiments showing that a reduction in dentate connectivity correlates with stress susceptibility in animals. Received: 17 February 1999 / Final version: 23 August 1999     

Fluoxetine suppresses palatability-induced ingestion

Non-deprived rats were allowed 1-h access to a range of saccarin solutions from 0.001 to 0.1 M Na saccharin. Compared to a group of rats drinking tap water, the rats drinking the saccharin solutions ingested a great deal more fluid, with as much as 24–30 ml consumed of the 0.01 M concentration, compared to 3–5 ml in controls. Fluoxetine (IP) decreased this palatability-induced excessive consumption in a dose-related manner. Effects of 10 mg/kg fluoxetine were apparent for 48 h after injection. This effect on palatability-induced ingestion may relate to previously reported effects of fluoxetine on food consumption.     

氟西汀和阿米替林对大鼠强迫游泳试验的行为表现及脑内信号分子ERK1/2磷酸化水平的影响

目的 观察氟西汀和阿米替林对大鼠强迫游泳试验中各种行为表现及脑内信号分子细胞外调节蛋白激酶(ERK1/2)磷酸化水平的影响. 方法 30只雄性SD大鼠先预游15 min.间隔23h后,按随机数字表法分成3组:氟西汀组、阿米替林组和对照组,每组各10只.氟两汀、阿米替林按20 mg/kg腹腔注射给药,对照组腹腔注射等体积的蒸馏水,1h后进行5 min的游泳测试,录像并记录出现不动行为的潜伏期和不动、游泳及攀抓行为的时间.游泳完毕后将大鼠灌流处死.对脑组织进行磷酸化ERK1/2(pERK1/2)免疫组织化学染色.观察pERK1/2阳性神经元在部分脑区的分布. 结果 (1)阿米替林组不动行为潜伏期明显长于对照组,攀抓行为时间明显长于对照组和氟西汀组,不动行为时间明显少于对照组;氟西汀组游泳行为时间明显长于对照组和阿米替林组;以上差异均有统计学意义(P<0.05).(2)氟西汀组前额皮质、扣带回及边缘前皮质脑区中pERK1/2阳性神经元数目较对照组和阿米替林组明显减少:阿米替林组腹外侧隔核中pERK1/2阳性神经元数目较对照组明显减少;两给药组下丘脑室旁核中pERK1/2阳性神经元数目较对照组均明显减少,其中阿米替林组减少幅度更大:以上差异均有统计学意义(P<0.05). 结论 阿米替林和氟西汀能对大鼠强迫游泳试验的行为表现产生不同影响,二者可能都有降低负性心理应激反应的作用.脑内ERK1/2信号通路可能参与其中.     

脑卒中急性期并发抑郁症88例临床分析

目的探讨脑卒中急性期并发抑郁状态的临床特点和治疗原则。方法回顾分析88例脑卒中急性期并发抑郁状态患者的主要临床特点,并观察百优解治疗2、4周时的疗效。结果脑卒中急性期并发抑郁状态的发生率为26.0%(132/507),其中多次卒中患者抑郁状态的发病率(46.9%)明显高于首次发病的患者(21.0%)(P<0.01)。病灶主要位于左半球的例数是右半球的2.95倍(65/22)。位于半球前部的例数是后部的1.90倍(57/30)。入组的88例,轻度抑郁68例(77.3%),中度抑郁14例(15.9%),重度抑郁6例(6.8%)。百优解结合心理治疗2周时汉密尔顿抑郁量表(HAMD)评分较治疗前有显著下降(P<0.05);4周时HAMD评分较2周时进一步下降(P<0.01)。结论脑卒中急性期抑郁状态发生率较高,多次卒中患者更加明显,病灶多位于左半球及半球的前部。积极抗抑郁治疗不但能使抑郁症状得到很大地改善,而且能促进卒中后神经功能的恢复。     

Long-term fluoxetine treatment decreases 5-HT1A receptor responsivity in obsessive-compulsive disorder

Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor with therapeutic benefit in patients with obsessive-compulsive disorder (OCD). To evaluate the effect of chronic FLX treatment on 5-HT_1A receptor responsivity, hypothermic, neuroendocrine, and behavioral responses to the selective 5-HT_1A receptor ligand ipsapirone (IPS) were examined in patients with primary OCD. A single dose of 0.3 mg/kg of IPS or placebo were given under double-blind, random-assignment conditions to ten patients before and during FLX treatment. The ability of IPS to induce hypothermia and ACTH/cortisol release was significantly attenuated during chronic FLX as compared to the pretreatment IPS challenge. The behavioral effects of IPS, though minimal, were less pronounced during FLX treatment. While FLX was effective in reducing the severity of OC symptoms, no significant correlation between attenuation of 5-HT_1A receptor-mediated functional measures and FLX-induced improvement in OC symptoms was detected. These findings are consistent with the development of adaptive hyporesponsivity of the 5-HT_1A receptor-effector system complex possibly involving subsensitivity of the 5-HT_1A receptor itself and/or decreased functional activity of the postreceptor signal transduction. Modulation of 5-HT_1A receptor-effector system function may be critical to the antidepressant/anti-OC efficacy of 5-HT reuptake inhibitors.Part of this work was presented at the 17th Congress of the CINP, Kyoto, Japan, September 10–14, 1990     

氟西汀联合多潘立酮治疗功能性消化不良临床观察

目的　观察氟西汀 (Fluoxetine)联合多潘立酮 (Domperidone)治疗功能性消化不良 (FD)临床疗效和安全性。方法　将 336例FD患者随机分为A组和B组各 16 8例 ,两组均予多潘立酮 10mgtid治疗 ,B组加服氟西汀 2 0mgqd(早晨与食物同服 ) ,疗程均为 4周。全组病例观察治疗前后临床疗效。 结果　A组临床显效率 2 2 6 % ,总有效率 4 8 8% ;B组临床显效率 4 4 6 % ,总有效率 84 5 % ;总有效率B组明显高于A组(P <0 0 1)。结论　氟西汀联合多潘立酮治疗FD疗效优于单用多潘立酮     

芪参复康胶囊与氟西汀治疗抑郁症疗效观察研究

目的通过比较纯中药制剂芪参复康胶囊与氟西汀治疗抑郁症疗效比较，观察芪参复康胶囊治疗抑郁症疗效。方法65例符合CCCMD-2-R及DSM-Ⅲ-R诊断标准抑郁症患者，HAMDRS得分≥20，经6周对照观察研究，HAMDRS，CGL，TESS量表及临床疗效评估。结果芪参复康胶囊治疗抑郁症疗效肯定，显效率68．5％，比氟西汀76．5％略低，两者无显著性差异，芪参复康胶囊不良反应较氟西汀少而轻。结论纯中药制剂芪参复康胶囊治疗抑郁症疗效肯定，不良反应轻，依从性好。     

Cluster of MMPI personality profiles in chronic tension-type headache and predictable response to Fluoxetine

A study was made of the personality profiles of a sample of 51 patients with chronic tension-type headache (CTH) employing the Minnesota Multiphasic Personality Inventory (MMPI). Two clusters were obtained by applying multivariate classification techniques: cluster 1 (with elevations on scales Hy, D and Hs only) and cluster 2 (exhibiting elevations on most scales except Pd, Mf and Si). Fifty subjects without chronic pain or known psychiatric disorders, and extracted from the same social setting as the patients, completed the MMPI as a control group. Fluoxetine treatment was started in the CTH group, with follow-up over a 1-year period. Chi-squared analysis correlating the clusters obtained to different pain-related variables and epidemiological parameters revealed a significant association to sex only. There were no differences in therapeutic response between the two clusters. However, the patients belonging to the less perturbed cluster who exhibited profiles analogous to those of the control population showed significant improvement with respect to the global sample and their own cluster.