Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem,caudate/putamen and cortex,and on dopamine D1 and D2 receptors in the caudate/putamen

Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D₁ (³[H]SCH 23390) and D₂ (³[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither³[H]SCH 23390 nor³[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.     

磁刺激运动诱发电位在腰椎间盘突出所致的腰骶神经根病变中的应用研究

在35例有L5和／或S1神经根损害表现的腰椎间盘突出患者腰椎区进行磁刺激运动诱发电位（MEP）检查，测定、记录胫前肌、展肌和小趾展肌MEP的起始潜伏期（OL）。结果显示，35例中至少有一条总侧肌肉MEP异常33例（94．3％）。在L4－5椎间盘突出中，以胫前肌的MEP异常为主；在L5－S1椎间盘突出中，以小趾展肌的MEP异常为主。表明腰椎区MEP检查对腰椎间盘突出所致的腰骶神经根病变较为敏感，可为临床诊断提供可靠依据并有助于定位诊断。     

Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: effects of dopamine antagonist,cholinomimetic, sedative and stimulant drugs

This experiment was undertaken to provide a pharmacological characterization of performance on a task involving food-related instrumental and consummatory behavior. Rats were tested in an operant chamber in which there was a choice between pressing a lever to receive a preferred food (Bioserve pellets) or approaching and consuming a less-preferred food (Lab Chow). The lever pressing schedule was a fixed ratio 5 (FR5). Rats usually pressed the lever at high rates to obtain the preferred food, and typically ate little of the lab chow even though it was freely available in the chamber concurrently with the lever pressing schedule. Previous work has shown that injection of dopamine (DA) antagonists, or depletion of DA in the nucleus accumbens, caused a substantial shift in behavior such that lever pressing was reduced but chow consumption increased. In the present study it was shown that the DA antagonist haloperidol decreased lever pressing and increased chow consumption at doses of 0.1 and 0.15 mg/kg. The D1 antagonist SCH 23390 (0.05, 0.1 and 0.15 mg/kg) and the non-selective DA antagonistcis-flupenthixol (0.3 and 0.45 mg/kg) decreased lever pressing and produced substantial increases in chow consumption. The D2 antagonist sulpiride decreased lever pressing, but produced only slight increases in chow intake at the highest dose. Pentobarbital reduced lever pressing and increased chow consumption at 10.0 mg/kg. The muscarinic agonist pilocarpine produced dose-related decreases in lever pressing, but failed to increase chow consumption. Amphetamine produced dose-related decreases in both lever pressing and chow consumption. These results indicate that low/moderate doses of the DA antagonists haloperidol,cis-flupenthixol and SCH 23390 can suppress lever pressing in doses that leave the animal directed towards food acquisition and consumption.     

Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson''s disease patients

Cortical excitability of the primary motor cortex is altered in patients with Parkinson's disease (PD). Therefore, modulation of cortical excitability by high frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex might result in beneficial effects on motor functions in PD. The present study aims to evaluate the effect of rTMS of the motor cortex on motor functions in patients with PD. Thirty-six unmedicated PD patients were included consecutively in this study. The patients were assigned in a randomized pattern to one of two groups, one group receiving real-rTMS (suprathreshold 5-Hz, 2000 pulses once a day for 10 consecutive days) and the second group receiving sham-rTMS using closed envelopes. Total motor section of Unified Parkinson's Disease Rating Scale (UPDRS), walking speed, and self-assessment scale were performed for each patient before rTMS and after the first, fifth, 10th sessions, and then after 1 month. Evaluation of these measures was performed blindly without knowing the type of rTMS. anova for repeated measurements revealed a significant time effect for the total motor UPDRS, walking speed and self-assessment scale during the course of the study in the group of patients receiving real-rTMS (P = 0.0001, 0.001, and 0.002), while no significant changes were observed in the group receiving sham-rTMS except in self-assessment scale (P = 0.019). A 10-day course of real-rTMS resulted in statistically significant long-term improvement of the motor functions in comparison with the sham-rTMS. The rTMS could have a therapeutic role of for PD patients.     

Movement-related potential measures of different modes of movement selection in Parkinson's disease

Movement-related potentials were recorded preceding self-paced voluntary movements in patients with Parkinson's disease and in healthy subjects of the same age group. We compared the Readiness Potential preceding joystick movements in a fixed direction and preceding joystick movements in freely selected directions. In normal subjects the Readiness Potential amplitude was higher preceding freely selected movements than preceding movements in a fixed direction. The Readiness Potential in Parkinson patients failed to be modified by the different modes of movement selection. The modulation of the Readiness Potential by different ways of preparing for movement might be due to the supplementary motor area (SMA) being more strongly engaged by tasks requiring internal control of movements than by tasks that are externally structured. The results suggest that this task-dependent variation of SMA activity is reduced in Parkinson's disease. A failing capacity to adapt SMA activity to different task demands has previously been suggested by evidence from positron emission tomography studies using similar tasks.     

Pyramidal cells in primary auditory cortex project to cochlear nucleus in rat

Recent work has demonstrated that the auditory cortex in rat sends direct projections to the auditory nuclei of the brainstem, including the cochlear nucleus and superior olive. To determine the cortical origin of the projections to cochlear nucleus, Fast Blue, a retrograde fluorescent tracer, was injected into the cochlear nucleus. Labeled cells in the forebrain were then studied with light microscopy and mapped. The projection was found to originate from large pyramidal neurons in layer V of primary auditory cortex. The projection was predominantly ipsilateral, and no labeled neurons were found in other cortical areas. These data imply that primary auditory cortex exerts influence over ascending auditory information at the earliest stages of the central auditory system.     

帕罗西汀对抑郁模型大鼠不同脑区环磷酸腺苷反应元件结合蛋白的影响

目的探讨帕罗西汀在不同用药时间对抑郁模型大鼠海马、前额叶皮质环磷酸腺苷反应元件结合蛋白（CREB）磷酸化（p-CREB）及总蛋白（t-CREB）水平的影响。方法成年雄性SpragueDawley大鼠36只，随机分为6组：对照组、抑郁模型组（以下简称模型组）、抑郁模型＋用药1d组（以下简称用药1d组）、抑郁模型＋用药1周组（以下简称用药1周组）、抑郁模型＋用药2周组（以下简称用药2周组）和抑郁模型＋用药4周组（以下简称用药4周组），每组各6只。抑郁模型的制作为强迫大鼠游泳4周，每天1次，每次15min。帕罗西汀的剂量为10m∥kg体质量，灌胃给药，时间分别为1d和1，2，4周，每天1次，于每次游泳前用药。采用Westernblot法检测各组大鼠海马及前额叶皮质的p-CREB和t-CREB水平。结果（1）模型组及用药1d、1周组大鼠海马p-CREB水平明显低于对照组（P〈0．01），用药2，4周组大鼠海马p-CREB水平与对照组的差异无统计学意义（P〉0．05）；模型组及各用药组海马t-CREB水平与对照组的差异无统计学意义（P〉0．05）。（2）模型组及用药1d和1，2周组大鼠前额叶皮质p-CREB水平均明显低于对照组（P〈0．05），用药4周组与对照组的差异无统计学意义（P〉0．05）。模型组及用药1d、1周组大鼠前额叶皮质t-CREB水平与对照组的差异无统计学意义（P〉0．05），用药2，4周组大鼠前额叶皮质t-CREB水平均明显高于对照组（P〈0．05或P〈0．01）。结论慢性强迫游泳导致大鼠海马及前额叶皮质CREB活性降低，长期使用帕罗西汀可逆转此效应，提高抑郁大鼠前额叶皮质的CREB水平。     

Elevation of cell adhesion molecule immunoreactivity in the anterior cingulate cortex in bipolar disorder.

BACKGROUND: Neuroimaging reports of increases in signal hyperintensities in white and deep gray matter and other work indicate that there might be an inflammatory response in affective disorders. METHODS: The microvascular immunoreactivity of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 was measured with image analysis in postmortem tissue from the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) from 15 unipolar and 15 bipolar subjects and compared with each other and with 15 subjects with schizophrenia and 15 control subjects. RESULTS: Intercellular adhesion molecule-1 immunoreactivity in gray and white matter of the ACC in bipolar subjects was increased compared with control subjects (gray: p =.001; white: p <.001) and schizophrenic subjects (gray: p =.016; white: p =.025) and modestly increased in white matter compared with unipolar subjects (p =.049). No such differences were found in the DLPFC. CONCLUSIONS: These findings are consistent with the presence of an inflammatory response in the ACC in bipolar disorder.     

Effects of glucocorticoids on declarative memory function in major depression.

BACKGROUND: Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexamethasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). METHODS: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. RESULTS: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3. CONCLUSIONS: These findings are consistent with an altered sensitivity of declarative memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethasone-induced reductions in cortisol, in patients with MDD.     

氟西汀对2型糖尿病合并抑郁症患者下丘脑-垂体肾上腺轴功能及临床疗效的影响

目的探讨氟西汀对 2型糖尿病合并抑郁症患者的下丘脑 垂体 肾上腺轴 (HPA)功能的影响及其临床意义。方法测定 98例 2型糖尿病患者和 3 4例正常对照组基础血皮质醇 (F ,0 8:0 0am、16:0 0pm)、小剂量地塞米松抑制试验 (DST)后血F、2 4h尿游离皮质醇 (UFC)。将 64例 2型糖尿病伴发抑郁症患者随机分成A组 (服用氟西汀组 ,3 2例 )和B组 (未服用氟西汀组 ,3 2例 )。予 6周治疗。分别于治疗前、后进行HAMD评分及代谢控制水平评估。结果 ( 1)血F( 0 8:0 0am、16:0 0pm)、2 4h尿UFC、DST脱抑制例数2型糖尿病患者较正常对照组增高 (P <0 .0 1) ,2型糖尿病伴抑郁症组 (DD组 )较无抑郁症组 (DM组 )增高(P <0 .0 5 ,P <0 .0 1)。 ( 2 )经 6周治疗后 ,服用氟西汀组 (A组 )较未服用氟西汀组 (B组 )糖皮质激素水平降低 (P <0 .0 1)、HAMD评分降低 (P <0 .0 1) ,糖脂代谢改善 (P <0 .0 5 ,P <0 .0 1)。 ( 3 ) 2 4h尿UFC与HbA1C呈正相关性 (r =0 .5 69,P <0 .0 1)、IR呈正相关 (r =0 .65 3 ,P <0 .0 1)、与HAMD评分呈正相关性 (r =0 .3 5 2 ,P <0 .0 5 )。结论 2型糖尿病及合并抑郁症患者HPA轴功能紊乱 ,加重了糖代谢紊乱和胰岛素抵抗 ;氟西汀干预治疗抑郁症可改善抑郁症和糖脂代谢。