Evoked field potential analysis of dopaminergic mechanisms in the isolated turtle olfactory bulb

Dopaminergic mechanisms were Anatyzed in an isolated preparation of the turtle olfactory bulb. Field potentials were evoked by antidromic or orthodromic stimulation, and the effects determined of pharmacological manipulations of the bathing medium. In the presence of dopamine or a dopamine agonist, apomorphine, there was a reduction of amplitude and delay of onset of the component of the field potentials due to granule cell responses; fluphenazine, a dopamine antagonist, had generally opposite effects. Using paired volleys, it was found that the suppression of the response to the second test volley was reduced in the presence of dopamine or apomorphine, but enhanced in the presence of fluphenazine.The most likely explanation of these results is that exogenous dopamine depresses the response of mitral cells, which in turn decreases the dendrodendritic synaptic excitation of granule cells and reduces their inhibitory feedback onto mitral cells. This suggests that the dopaminergic cells in the bulb may suppress mitral cells by modulating excitable mechanisms in the mitral dendritic membrane, or modulating long-lasting synaptic potentials.     

Is there a non-dopaminergic nigrostriatal pathway?

Sixteen per cent of the substantia nigra cell bodies normally labeled from the injection of a fluorescent retrograde tracer in the caudate-putamen complex could still be labeled by the same procedure after multiple intracisternal 6-hydroxydopamine treatments that depleted dopamine levels in the caudate-putamen complex to 1.0% of control. However, the demonstration of glyoxylic-acid-induced catecholamine histofluorescence in tissue from these lesioned rats revealed that many of the surviving retrogradely-labeled substantia nigra cell bodies still contained dopamine. The persistence of some dopamine in the substantia nigra of the lesioned animals was confirmed biochemically. Therefore, retrograde tracing in 6-hydroxydopamine lesioned rats overestimated the extent of the non-dopaminergic nigrostriatal tract.The simultaneous combination of retrograde fluorescent tracing and catecholamine histofluorescence in unlesioned animals revealed that only 5% or less of the substantia nigra cell bodies retrogradelylabeled from the caudate-putamen complex were without catecholamine fluorescence. These apparently non-dopaminergic nigrostriatal cells were located primarily in the ventral tegmental area, substantia nigra pars reticulata and extreme medial edge of the substantia nigra pars compacta.     

Chlorimipramine,electroconvulsive shock and combination thereof: Differential effects of chronic treatment on apomorphine-induced behaviours and on striatal and mesocortical dopamine turnover

Summary We studied the influence of different pretreatment regimens (Chlorimipramine-Cmi, electroconvulsive shock-ECS, and Cmi+ECS all regimens being applied for either 2 or 15 days) on the open field behaviour, on the striatal and on the prefrontal dopamine-PFC DA turnover in rats injected with either apomorphine-AP 25 g/kg (stimulating presynaptic DA receptors), AP 200 g/kg (stimulating postsynaptic DA receptors), or vehicle (control).In the controls, AP 25 g/kg reduced the locomotor activity and the striatal, but not the PFC DA turnover. AP 200 g/kg increased the locomotor activity and reduced the striatal but not the PFC DA turnover.Short-term pretreatment: ECS and Cmi+ECS prevented the decrease of striatal DA turnover after AP 25 g/kg. No other influence of any pretreatment on behaviour or DA-turnover became significant.Long-term pretreatment: Chronic Cmi: marginally increased the open field behaviour and marginally decreased the PFC DA turnover; significantly increased the effect of AP (200 g/kg) on striatal DA turnover and the effect of AP (25 and 200 g/kg) on PFC DA turnover. Repeated ECS: decreased locomotion and rearing and increased PFC DA turnover; increased the effect of AP (200 g/kg) on locomotion and on striatal DA turnover; decreased the effect of AP (25 and 200 g/kg) on PFC DA turnover.Chronic Cmi+ECS: decreased locomotion and rearing and marginally decreased PFC DA turnover; increased the effect of AP on hyperlocomotion and on striatal DA turnover. No other influence of any chronic pretreatment on behaviour or on DA turnover became significant.The data support the view that chronic AD therapies increase DAergic functions related to postsynaptic rather than to presynaptic structures. It is suggested that the different effects of chronic Cmi and repeated ECS on AP-evoked PFC DA turnover help to understand the different influences exerted by both treatments on rats' behaviour.     

Reflections on experimental and human pathology of aggression

On the basis of the already proposed distinction between "normal" and "pathological" aggression in laboratory animals, it is essayed an integration of the experimental findings derived from a specific animal model of aggression with the available clinical information on human violent behavior. The too disregarded importance of the role played by the inhibitory control of brain functions, appears instead reportedly essential in the regulation of emotions and behavior, and is of great relevance in explaining the behavioral changes that follow induced or spontaneous impairment of the serotonergic system of the brain. As a matter of fact, the numerous evidences indicate that genetic predisposition and induced or acquired defects of serotonergic inhibitory control greatly concur to precipitate anomalous strong aggression. Interestingly, the cluster of symptoms presented by laboratory rats in consequence of the serotonergic discontrol, has many unexpected similarities with several pathological conditions of man. This fact confers to laboratory experiments the value of a tool aimed at a better understanding of the biological mechanisms which underlie corresponding alterations of human conduct, with special reference to pathological aggression and violence. In this line, some specific nutrient defects and/or malabsorption conditions can be important in the facilitation or elicitation of mental illness including human aggression. In addition, the efficacy and neurochemical action of those substances capable to partially or completely block or prevent experimental aggression, will likely assume equal relevance in the management or prevention of human violent behavior.     

和胃安神方对失眠模型大鼠5-羟色胺、多巴胺及去甲肾上腺素水平的影响

目的：探讨和胃安神方对失眠模型大鼠下丘脑5-羟色胺（5-HT）、多巴胺（DA）和去甲肾上腺素（NE）水平的影响。方法：将60只雄性Wistar大鼠随机分为6组,即正常对照组、失眠模型组、地西泮组、和胃安神方低剂量组、和胃安神方中剂量组、和胃安神方高剂量组。采用酶联免疫吸附试验（ELISA）检测各组大鼠下丘脑组织5-HT、DA、NE的水平。结果：与正常对照组比较,失眠模型组大鼠5-HT水平显著下降,差异有统计学意义（P<0.05),DA、NE水平较正常对照组显著升高,差异有统计学意义（P<0.05);与失眠模型组比较,地西泮组、和胃安神方低剂量组5-HT、DA、NE水平差异均无统计学意义(均P>0.05);和胃安神方中剂量组、和胃安神方高剂量组5-HT水平均较失眠模型组显著升高,差异有统计学意义(P<0.05),DA、NE水平较失眠模型组显著下降,差异有统计学意义（P<0.05)。结论：和胃安神方治疗失眠症的疗效机制可能与调节脑内5-HT、DA、NE水平有关。     

四物汤与十全大补汤的抗突变作用研究

用姐妹染色单体互换技术检测中药方剂四物汤、十全大补汤，发现其能明显降低环磷酰胺所致的ＳＣＥ值升高，表明有抗突变作用。     

Effects of drug history on the acquisition of responding maintained by GBR 12909 in rhesus monkeys

The reinforcing effects of cocaine have been associated with its actions at the dopamine reuptake site. Previous studies have shown that selective dopamine reuptake inhibitors can attenuate cocaine self-administration in animals, suggesting that they may serve as pharmacotherapeutic agents. In order to assess the potential reinforcing effects of one of these agents, the acquisition and maintenance of GBR 12909 self-administration were studied in different groups of rhesus monkeys (Macaca mulatta) that were either experimentally naive or experienced with respect to the self-administration of cocaine or GBR 12909. Lever-pressing was maintained under a multiple FR30 schedule with alternating components of either food or drug presentation. Experimentally naive monkeys failed to self-administer low doses of GBR 12909 (3–30 µg/kg per injection). However, after a history of cocaine self-administration, GBR 12909 (56 µg/kg per injection and then 30 µg/kg per injection) maintained numbers of drug deliveries similar to those maintained by cocaine. When another group of experimentally-naive monkeys was initially exposed to GBR 12909 self-administration, 56 µg/kg per injection failed to maintain responding. However, subsequent exposure to 100 µg/kg per injection established GBR 12909 self-administration, and high levels of responding were sustained later when the unit dose was decreased to 30 µg/kg per injection. In monkeys with prior experience with cocaine self-administration (75 sessions) unit doses of either 30 µg/kg per injection or 56 µg/kg per injection GBR 12909 maintained responding. In another group of monkeys with a more extensive history of cocaine self-administration (320 sessions), unit doses of either 10 µg/kg per injection or 30 µg/kg per injection GBR 12909 maintained responding. These results show that drug-maintained responding can be established with higher unit doses of GBR 12909. After exposure to these higher, more effective doses of GBR 12909, or effective doses of cocaine, lower doses of GBR 12909 are more likely to support drug-maintained responding.     

In situ and immunocytochemical localization of E-FABP mRNA and protein during neuronal migration and differentiation in the rat brain

The present study compares the temporal-spatial expression and tissue localization of the rat epidermal type fatty acid binding protein (E-FABP) (DA11/C-FABP/S-FABP/LEBP/KLBP) in the developing rat central nervous system (CNS). In situ hybridization (ISH) and immunocytochemistry (ICC) studies demonstrate that mRNA E-FABP and protein are expressed at high levels during neurogenesis, neuronal migration, and terminal differentiation. Migrating pyramidal cells in the cerebral cortex, Purkinje cells and deep nuclear neurons in the cerebellum, and neurons in the olfactory bulb and retina exhibited a strong E-FABP-like immunoreactivity (E-FABP-LI) throughout the entire process of differentiation and migration. The levels of E-FABP mRNA and protein were dramatically higher in prenatal and early postnatal neurons, as compared to adult neurons. The E-FABP antibody immunoreacted with growing neurites, and nuclear and cytoplasmic regions of neurons. The intracellular multiregional pattern of localization of E-FABP and its differential temporal expression during development, are consistent with its proposed role in transporting long chain free fatty acids and/or other hydrophobic ligands during neuronal differentiation and axon growth.     

孕妇广泛焦虑障碍和血浆DA、NE、5-HT的相关研究

目的 :探讨分娩前孕妇广泛性焦虑障碍与血浆 5 - HT、DA、NE的关系。方法 :首先用心理卫生量表 (SAS、SDS、HAMA、HAMD)筛查孕妇中存在广泛性焦虑和抑郁共病共 4 6例。研究组血浆中五羟色胺 (5 - HT4 6例 )、去甲肾上腺素 (NE4 6例 )、多巴胺 (DA4 5例 )和正常对照组 (5 - HT、DA、NE各 2 0例 )由苏州大学生化工程研究所采用高效液相色谱仪、电化学检测器进行测定。结果 :分娩前孕妇广泛性焦虑障碍血浆 5 - HT、DA、NE和对照组未见明显差异。讨论 :我们在产前经 SAS、HAMA检测发现产前孕妇广泛性焦虑障碍有 74例。我们选择了资料完整诊断明确的产前广泛性焦虑进行了血浆 5 - HT、NE、DA测定结果发现与对照组没有明显差异 ,这说明孕妇在临床上焦虑症状明显 ,但体内血浆神经介质极不稳定 ,神经介质变化在人体内较为复杂 ,使两者没有变化 ,提示孕妇广泛性焦虑障碍患者存在外周交感神经兴奋性增高 ,血浆 5 - HT、NE、DA浓度不能鉴别焦虑症。以上观点还需进一步研究。在妇产科广泛焦虑障碍这一疾病 ,应引起产科医师注意。