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.     

Cardiovascular collapse during anesthesia in a patient with preoperatively discontinued chronic MAO inhibitor therapy

We describe a patient in whom long-term monoamine oxidase (MAO) inhibitor therapy was discontinued 20 days before surgery with general anesthesia. This patient developed severe perioperative hypotension after administration of 10 mg of bupivacaine through an epidural catheter, which was corrected only after potent vasopressor therapy. We attribute this hemodynamic instability to attenuation of this patient's sympathetic tone based on several mechanisms: (1) residual effect of long-term administration of MAO inhibitor that caused a decrease in the number of β-adrenergic receptors (adrenergic subsensitivity due to receptor down-regulation), (2) recovered MAO activity causing effective degradation of sympathetic amines, and (3) combined attenuating effects of general and epidural anesthesia on sympathetic tone.     

A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action.

Data now exist from which an accurate definition for serotonin toxicity (ST), or serotonin syndrome, has been developed; this has also lead to precise, validated decision rules for diagnosis. The spectrum concept formulates ST as a continuum of serotonergic effects, mediated by the degree of elevation of intrasynaptic serotonin. This progresses from side effects through to toxicity; the concept emphasizes that it is a form of poisoning, not an idiosyncratic reaction. Observations of the degree of ST precipitated by overdoses of different classes of drugs can elucidate mechanisms and potency of drug actions. There is now sufficient pharmacological data on some drugs to enable a prediction of which ones will be at risk of precipitating ST, either by themselves or in combinations with other drugs. This indicates that some antidepressant drugs, presently thought to have serotonergic effects in animals, do not exhibit such effects in humans. Mirtazapine is unable to precipitate serotonin toxicity in overdose or to cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and moclobemide is unable to precipitate serotonin toxicity in overdose. Tricyclic antidepressants (other than clomipramine and imipramine) do not precipitate serotonin toxicity and might not elevate serotonin or have a dual action, as has been assumed.     

老年大鼠脑内肾上腺素能神经递质系统的变化

本文从下丘脑、大脑皮层、海马等脑区去甲肾上腺素(NA)的含量,其合成酶与降解酶的活性、NA受体数目等多环节的测定来分析肾上腺素能神经递质系统在老化脑中的变化。实验结果表明衰老过程下丘脑、大脑皮层内NA合成酶活性没变化,NA含量明显增高,下丘脑内α_1受体数目显著减少。上述结果提示这些脑区肾上腺素能神经的活动有可能减弱。同时,海马内单胺氧化酶B(MAO B)活性明显增加,说明海马神经元外组织有增生的可能。泰文并讨论了这些变化与老年记忆、行为与神经内分泌等脑功能衰退的关系。     

骨髓间充质干细胞体外诱导为神经细胞的研究

本实验观察了大鼠MSCs向神经细胞方向的诱导分化情况,以期为MSCs在神经移植领域的临床应用提供理论基础。用含10 ng／ml bFGF+20％FBS的DMEM对MSCs进行预诱导24 h后,以含200μmol／L的BHA+2％DMSO的无血清DMEM对MSCs进行诱导,观察诱导后细胞的光、电镜形态学变化,通过免疫组织化学法对诱导后细胞进行神经细胞表型及神经递质合成酶鉴定。结果显示:MSCs经BHA和DMSO诱导后,80％以上的细胞表现出神经元样形态,胞浆内可见较多Nissl体,并表达nestin、NSE、NF、MAP、SYN,部分诱导后的细胞表达ChAT、TH、GAD;电镜下观察,诱导后细胞核大而圆,核仁明显,胞浆内细胞器发达,可见大量粗面内质网和游离核糖体。提示,MSCs体外可被诱导分化为神经元样细胞,诱导后的细胞有合成某些神经递质的能力并具有发育早期神经元的超微结构特点。     

PEPTIDES AS NEUROTRANSMITTERS IN VASCULAR AUTONOMIC NEURONS

1. Neuropeptides are present in the majority of autonomic neurons projecting to blood vessels, where they are co-localized with non-peptide transmitters and sometimes with other peptides. 2. Neuropeptides are released from vasoconstrictor and vasodilator nerve terminals after high frequency stimulation (>2–5 Hz) with trains of impulses. 3. Neuropeptides can have potent post-synaptic effects on vascular tone, but often these effects are restricted to selected regions of the vasculature. 4. Post-synaptic effects of neuropeptides tend to be more slowly-developing and more long-lasting than those of non-peptide transmitters. 5. Autonomic vasoconstrictor and vasodilator responses often have multiple phases, with the faster phases being mediated by non-peptide transmitters and the slower phases mediated predominantly by one or more neuropeptides. 6. Some neuropeptides do not seem to have post-synaptic effects in a particular vascular bed, but can have presynaptic actions on neurotransmitter release. 7. Neuropeptides form an important component of the repertoire of neurotransmitters used by vascular autonomic neurons to regulate regional blood flow in response to a range of physiological stimuli.     

Control of feeding and sexual behaviors by neuropeptide Y: physiological implications

Recent evidence suggests that a variety of hypothalamic neuropeptides may mediate interneuronal communication to coordinate diverse neuroendocrine and behavioral functions. In this work, we describe the effects of neuropeptide Y (NPY) on feeding and sexual behaviors. We observed that central administration of bolus NPY stimulated a robust, dose-related feeding response in satiated male and female rats. Continuous NPY receptor activation also evoked dose-related, intermittent feeding in a manner normally observed during nocturnal feeding. It appears that the paraventricular nucleus in the hypothalamus may be the primary site of NPY action because the anticipated reciprocal changes in NPY concentrations, in response to food deprivation followed by ad libitum food intake, occurred only in this site. Additional findings revealed that NPY-induced feeding may follow either substantial reduction or complete restraint of an inhibitory influence on feeding mediated by alpha 2-adrenoreceptor systems in satiated rats. Further, NPY was found to suppress male and female sexual behaviors. The suppressive effects on sexual behavior were apparent prior to or at the time of the onset of feeding after NPY administration. These observations may provide a neurochemical basis for clinical and animal studies on disorders of feeding associated with diminished reproductive functions.     

甲乙型肝炎血清MAO同工酶活性变化研究

用荧光分光光度法检测了血清单胺氧化酶（ＭＡＯ）同工酶Ａ（ＭＡＯ－Ａ）和同工酶Ｂ（ＭＡＯ－Ｂ）活性，结果表明血清ＭＡＯ－Ｂ活性急性期甲肝组较正常对照组显著升高，慢性期乙肝极显著升高；二型肝炎组的ＭＡＯ－Ａ活性升高程度无统计学意义。二型肝炎ＭＡＯ同工酶活性改变与其它肝功生化指标无明显相关性，表现血清ＭＡＯ同工酶活性与肝功损害程度不相关。     

绞股蓝总皂甙(GPS)对大鼠脾脏淋巴细胞增殖功能的影响及其与去甲肾上腺素及皮质酮的关系(英文)

本文以神经内分泌免疫调节网络学说及祖国医学的整体观为指导思想,研究观察了我国民间常用草药绞股蓝的活性成分——绞股蓝总皂甙(GPS)对大鼠脾脏淋巴细胞增殖功能的影响及其与下丘脑,脾脏去甲肾上腺素(NE)以及血浆皮质酮的相互关系,结果表明,大鼠ip GPS,10及20 mg·kg·d~(-1)共7d,其脾细胞对丝裂原Con A诱导的增殖反应明显增强,以10 mg·kg·d~(-1)剂量组更为显著,同时,以高效液相色谱电化学检测器测定单胺类神经递质的结果表明,下丘脑NE含量下降,脾脏NE亦明显降低,与脾细胞增殖反应呈负相关;此外,血浆皮质酮水平下降,结果提示,GPS对免疫反应的影响,与作用于神经内分泌免疫调节网络,进而发挥免疫增强作用具有密切关系。     

老龄大鼠膀胱逼尿肌对神经递质反应的研究

目的 探讨老年排尿功能障碍的神经机制。方法 利用水浴条件下离体逼尿肌条张力测定技术，观察老龄Wistar大鼠膀胱逼尿肌条对不同浓度卡巴可、去甲肾上腺素、ATP的收缩反应改变；阿托品对卡巴可诱导逼尿肌收缩的舒张反应改变；异丙肾上腺素对电刺激诱导逼尿肌收缩的舒张反应改变。结果 与青龄组相比，老龄大鼠膀胱逼尿肌对ATP的收缩反应显著增强，对异丙肾上腺素的舒张反应在高浓度时增强；对卡巴可、阿托品、去甲肾上腺素的反应没有差异。结论 老龄大鼠排尿功能障碍可能与β-肾上腺素能、嘌呤能神经改变有关。