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.     

Dopaminergic agents differentially alter β-endorphin processing patterns in the rat pituitary neurointermediate lobe

We have established the content and molecular species of immunoreactive β-endorphin (ir-β-END) and immunoreactive N-acetyl-endorphin (ir-Nac-END) in rat neurointermediate lobe by specific radioimmunoassay (RIA) and high-performance liquid chromatography after chronic administration of dopamine (DA) agonists and antagonists. The DA agonist, bromocriptine, reduces tissue levels of all major immunoreactive species, in particular the C-terminally shortened N-acetylated forms. The DA antagonist, haloperidol, proportionally increases all immunoreactive forms, except Nac-β-END_1–27, thus altering the relative abundance of this species. These data indicate that DA is involved in the control of both tissue levels and processing of β-END-like peptides in the rat neurointermediate lobe.     

大鼠骨髓间充质干细胞向多巴胺样神经细胞分化

目的探索大鼠骨髓间充质干细胞向多巴胺能样细胞分化。方法全骨髓培养法分离大鼠骨髓间充质干细胞;体外培养至第3代,用碱性成纤维细胞生长因子,抗坏血酸和表皮生长因子诱导分化;免疫荧光法鉴定胞质中的多巴胺神经元相关蛋白的表达;RT-PCR鉴定多巴胺神经元相关基因的表达;ELISA法检测上清及胞质中的多巴胺。结果诱导后,免疫荧光法检测到诱导后的细胞表达多巴胺神经元相关蛋白:酪氨酸羟化酶、多巴胺转运蛋白和神经核蛋白;RT-PCR检测到诱导后的细胞表达多巴胺神经细胞相关基因TH、AADC;ELISA法检测到诱导后的上清及胞质中有多巴胺分泌。结论间充质干细胞具有向多巴胺能样细胞分化的能力。     

Substance P modulation of dopamine in the nucleus accumbens

Rats were implanted with bilateral injection cannulae in the nucleus accumbens. While microinjection of substance P (1.0-10.0 micrograms/side) did not alter locomotor or rearing behavior, it did potentiate the motor stimulant effects of intra-accumbens injection with dopamine. Further, substance P injection into the nucleus accumbens significantly elevated the levels of dopamine metabolites in that nucleus. Both the behavioral and neurochemical dose-response curves were biphasic, with 3.0 micrograms of substance P producing a maximal response. These data suggest an interaction between substance P and dopamine in the nucleus accumbens.     

Dopamine receptor properties in Parkinson''s disease and Huntington''s chorea evaluated by positron emission tomography using 11C-N-methyl-spiperone

Dopaminergic receptor properties in the striatum of patients with Parkinson's disease (PD) and Huntington's chorea (HD) were studied by positron emission tomography (PET), using 11C-N-methyl-spiperone as a dopamine D2 receptor ligand. The time-dependent regional radioactive uptake in the caudate nucleus and the putamen was measured and fitted to a 3-compartment pharmacokinetic model. The rate constant k3 for specific binding to the receptor compartment in the striatum was determined in relation to the binding in regions with a low density of specific binding sites, such as the cerebellum and the frontal cortex . k3, which is a measure of the receptor density, was reduced in one patient with HD but less affected in PD in comparison with healthy controls. The pattern of k3 values calculated from the 6 PD patients is discussed in relation to any side-to-side differences in dopamine receptor densities in hemiparkinsonism and to possible "hypersensitivity" of dopamine receptors in the early stage of the disease and down-regulation in more advanced disease.     

Striatal membrane-bound and soluble catechol-O-methyl-transferase after selective neuronal lesions in the rat

Summary Activities of the two forms of catechol-O-methyltransferase (COMT), viz. the soluble (S-COMT) and the membrane-bound (MB-COMT), have been studied in the rat striatum to characterize their localization in relation to the nigrostriatal dopaminergic neurons. Selective unilateral nigrostriatal dopaminergic lesions were produced by an intranigral injection of 6-hydroxydopamine (6-OHDA; 8g/site). 6-OHDA caused an extensive lesion of the dopaminergic neurons as revealed by non-detectable concentrations of dopamine in the striata of the lesioned sites. In spite of that neither S-COMT nor MB-COMT activities were altered in comparison with the intact control striata. The intrastriatal injection of kainic acid significantly increased S-COMT activity but to some extent decreased MB-COMT activity. Kainic acid did not alter the striatal concentration of dopamine.These results suggest that both S-COMT and MB-COMT reside postsynaptically the nigrostriatal dopaminergic neurons. S-COMT seems to be found mainly in striatal glial cells, whereas striatal MB-COMT might be located both in postsynaptic neuronal and extraneuronal cells.     

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.     

Inhibitory dopamine receptors on sympathetic neurons innervating the cardiovascular system of the pithed rat

Summary Additional experimental evidence was obtained for an inhibitory function of prejunctional ₂-adrenoceptors and/or dopamine receptors located on noradrenergic neurons innervating the heart and resistance vessels of the pithed normotensive rat. Mixed ₂-adrenoceptor receptor agonists, differing in selectivity towards either receptor type, i.e. N,N-di-n-propyldopamine (DPDA), 2-N, N-di-n-propylamino-6, 7-dihydroxy-1,2,3,4-tetrahydronaphthalene (DP-6,7-ADTN), B-HT 920 and B-HT 933 (azepexole) were used.In pithed normotensive rats, DPDA (30 and 100 g/kg/min) dose-dependently inhibited the electrical stimulation-induced increase in diastolic pressure, but did not significantly affect the stimulation-evoked increase in heart rate. The inhibition exerted by DPDA was blocked by haloperidol and sulpiride (0.3 mg/kg of each), but not by yohimbine (1 mg/kg), indicating the involvement of dopamine receptors. In this respect, sulpiride and haloperidol were found approximately equipotent.DP-6,7-ADTN (10 and 30 g/kg/min) impaired both tachycardic and vasoconstrictor responses in a dose-dependent manner. Sulpiride (0.3 mg/kg) only partially restored the DP-6,7-ADTN-depressed stimulation-evoked increase in diastolic pressure, whereas yohimbine (1 mg/kg) alone was without effect. The combination of both antagonists completely prevented the inhibition caused by DP-6,7-ADTN. On the other hand, yohimbine (1 mg/kg), but not sulpiride (0.3 mg/kg), selectively antagonized the DP-6,7-ADTN-induced inhibition of stimulation-evoked tachycardia.B-HT 920 (1, 3 and 10 g/kg/min) very effectively reduced the increase in diastolic pressure and heart rate caused by electrical stimulation. Inhibitory dopamine as well as ₂-adrenoceptors participated in the vascular effects of B-HT 920, whereas ₂-adrenoceptors were only involved in the cardioinhibitory response to this agonist.B-HT 933 (0.6 and 1 mg/kg/min) dose-dependently reduced the stimulation-evoked increase in arterial pressure through selective stimulation of inhibitory ₂-adrenoceptors, dopamine receptors not taking a part.The results confirm and extend the observations that in addition to ₂-adrenoceptors inhibitory dopamine receptors are located on the sympathetic neurons connected with the arterial vasculature of the pithed normotensive rat. The sympathetic nerves innervating the rat heart do not contain inhibitory dopamine receptors; their activity only can be modulated by ₂-adrenoceptor stimulation. In the pithed normotensive rat, activation of prejunctionally located ₂-adrenoceptors more effectively inhibits the sympathetic activity directed to the heart than that to the resistance vessels.     

原发性高血压患者红细胞[Ca2+]i浓度变化及影响因素

目的：观察原发性高血压患者红细胞[Ca^2 ]i,多巴胺β羟化酶及ATP含量变化并分析其结果。方法：测定35例高血压患者的红细[Ca^2 ]i、ATP、血清多巴胺β羟化酶活性,血糖及血浆胰岛素含量,并以30例健康成年人为对照。结果：高血压患者的红细胞[Ca^2 ]i、ATP、多巴胺β羟化酶均明显高于对照组（P＜0．05,P＜0．01）,但血糖与胰岛素未见明显变化。结论：高血压患者血清多巴胺β羟化酶活性增强伴随ATP与[Ca^2 ]i升高。