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。     

补益中药对老龄雄性大鼠下丘脑神经递质——甲状腺轴机能作用的研究

本文通过对3月龄、18月龄、24月龄雄性大鼠下丘脑去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA),和下丘脑垂体促甲状腺释放激素(TRH)、垂体、血甲状腺释放激素(TSH)、血甲状腺激素(T_3、T_4)的测定,研究了大鼠下丘脑神经递质与甲状腺轴机能的增龄性变化,并在此基础上探讨了补益中药对老龄大鼠下丘脑—垂体—甲状腺机能的作用。结果提示:老龄大鼠下丘脑机能的减退是甲状腺轴机能减退的重要原因;补益中药可能改善了老龄大鼠下丘脑的调控机能,进而延缓了甲状腺轴机能的老年性变化。     

Effects of exposure to an estrous female on forebrain monoaminergic neurotransmission in the non-copulating male rat

Regional changes in the rate of brain monoamine synthesis were monitored in male rats exposed to, but prevented from physical contact with, an estrous or an ovariectomized female. The in vivo rate of tyrosine and tryptophan hydroxylase activities were estimated by measuring the accumulation of DOPA and 5-HTP following inhibition of cerebral aromatic l-amino acid decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015) treatment (100 mg/kg i.p.) 5 min upon NSD-1015 treatment, the males were exposed to an intact estrous female or an ovariectomized female for 20 min before decapitation and brain dissections. Exposure to an estrous female produced an increased rate of tyrosine and tryptophan hydroxylase activity in the medial prefrontal cortex, the dorso-lateral neostriatum and in the ventral neostriatum, in comparison with home-cage controls. By the same comparison, exposure to an ovariectomized female resulted in an increased rate of tyrosine hydroxylase activity in the medial prefrontal cortex, byt not in the neostriatal areas, whereas tryptophan hydroxylase activity was unaffected. Finally, exposure to the empty test cage, with no stimulus females present, did not produce any statistically significant changes in the rate of tyrosine or tryptophan hydroxylase activity in any of the brain areas sampled. Taken together with recent findings from this laboratory, the present results demonstrate that the level of sexual motivation brought about by the olfactory, auditory and/or visual stimulation of a receptive female is associated with an increased demand on catecholamine and 5-hydroxytryptamine synthesis in the limbic forebrain of the male rat. The finding that the presence of an unestrous female produced an enhanced demand on tyrosine hydroxylase activity in the medial prefrontal neocortex demonstrates that the sexual incentive provided by the estrous female may not be the only factor responsible for all the effects observed in the present study. In fact, there is a distinct possibility that the intense challenge produced by sexually significant stimuli is but an endpoint, and that the changes found in forebrain monoamine synthesis is a reflection of an environmental challenge not necessarily specifically linked to the sexual behavior.     

Quantification and pharmacological characterization of dialysate levels of noradrenaline in the striatum of freely-moving rats: release from adrenergic terminals and modulation by α2-autoreceptors

Information concerning striatal levels of noradrenaline (NA) remains inconsistent. Here we have addressed this issue using a sensitive method of HPLC coupled to amperometric detection. The NA reuptake-inhibitor, reboxetine, selectively elevated levels of NA versus dopamine (DA), and NA levels were also selectively elevated by the α₂-adrenoceptor (AR) antagonist, atipamezole. The actions of atipamezole were mimicked by the preferential α_2A-AR antagonist, BRL44408, while JO-1 and prazosin, preferential antagonists at α_2C-ARs, caused less marked elevations in NA levels. In contrast to antagonists, the α₂-AR agonist, S18616, decreased NA levels and likewise suppressed those of DA. Unilateral lesions of the substantia nigra with 6-hydroxydopamine depleted DA levels without affecting those of NA. Further, the D₃/D₂ receptor agonist, quinelorane, decreased levels of DA without modifying those of NA. However, the D₃/D₂ receptor antagonists, haloperidol and raclopride, and the DA reuptake-inhibitor, GBR12935, elevated levels of both DA and NA. Levels of 5-HT (but not of NA or DA) were increased only by the 5-HT reuptake-inhibitor, citalopram. They were decreased by S18616 and prazosin, reflecting the inhibitory and excitatory influence of α₂- and α₁-ARs, respectively, upon serotonergic pathways. In conclusion, NA in the striatum is derived from adrenergic terminals. Its release is subject to tonic, inhibitory control by α₂-ARs, possibly involving both α_2A- and α_2C-AR subtypes, though their respective contribution requires clarification. A role of dopaminergic terminals in the reuptake of NA likely explains the elevation in its levels elicited by DA reuptake-inhibitors and D₃/D₂ receptor antagonists.     

Morphologic analysis of rat retinocollicular neuron terminals containing monoamine oxidase

The retino-collicular neuron terminals containing type A monoamine oxidase (MAO-A) in the stratum griseum superficiale of the rat superior colliculus were analyzed to provide a morphologic basis for the physiologic role of these neurons in the visual pathway. A computer-assisted, three-dimensional re-construction of the terminal complex associated with the MAO-A-positive terminals was performed. MAO-A-positive terminals originated in the retina and terminated in the stratum griseum superficiale. This was confirmed by tract tracing and enucleation experiments. The terminals were densely grouped in clusters of irregularly shaped swellings. Electron microscopy revealed that the MAO-A-positive terminals were located in a glomerulus-like structure. In this terminal complex, a significant proportion of the axonal profiles (42.96%) synapsed with the MAO-A-positive terminals. Most of the profiles (24.16%) resembled presynaptic dendrites, which represent intermediate elements between the retinal terminals and conventional dendrites. Unlike the glomerulus in the dorsal lateral geniculate body, the MAO-A-positive terminal swellings were not located in the central part of the terminal complex. The terminals had an irregular shape and were located in the complex. The terminal complex was partially ensheathed by glial processes. Furthermore, the membrane surfaces exhibiting synaptic specializations were very small compared with the total surface of the terminal swellings. The membrane length of the synaptic specialization was 5.38% of the total perimeter of the MAO-A-positive terminals.     

Enrichment of Glutamate-like Immunoreactivity in Primary Afferent Terminals Throughout the Spinal Cord Dorsal Horn

Although several lines of evidence indicate that glutamate is a neurotransmitter in primary afferent terminals, controversies exist on the proportion and types of such terminals that release glutamate. In the present study quantitative analysis of immunogold labelling was used to assess the presence of glutamate-like immunoreactivity in primary afferent terminals in laminae I – V of the rat spinal cord dorsal horn. Anterograde transport of choleragenoid – horseradish peroxidase from a spinal ganglion and tetramethyl benzidine histochemistry were used to identify primary afferent terminals in laminae I and III – V. Presumed C-fibre terminals in lamina II were identified on morphological criteria (dense sinusoid axon terminals). Primary afferent terminals in all dorsal horn laminae displayed significantly higher levels of glutamate-like immunoreactivity than pleomorphic vesicle-containing profiles in laminae III – IV and large neuronal cell bodies in laminae III – V. The density of gold particles over primary afferent terminals also significantly exceeded the average density of gold particles over laminae II and III – IV. The highest densities of gold particles were present over dense sinusoid axon terminals in lamina II. These findings suggest that glutamate, alone or in combination with other neuroactive compounds, is involved in the transfer of all sensory modalities from primary afferent fibres to dorsal horn neurons.     

Selective inhibition of MAO-A,not MAO-B,results in antidepressant-like effects on DRL 72-s behavior

The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (–)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects.     

Monoamine oxidase inhibition as a sequel of hydrogen sulfide intoxication: increases in brain catecholamine and 5-hydroxytryptamine levels

Administration of sodium hydrosulfide (NaHS), an alkali salt of hydrogen sulfide (H₂S) at doses of 10 and 30 mg/kg, corresponding to sublethal and lethal doses (0.66 and 2.0 X LD₅₀) resulted in significant increases in regional catecholamine levels of the rat brain only after the dose of 2.0 × LD₅₀ of NaHS. Whereas the cortex and the cerebellum showed little or no change in catecholamine content, the hippocampus, striatum and brainstem all showed increases in noradrenaline and adrenaline. Additional analysis also showed that brainstem dopamine and 5-hydroxytryptamine levels (5-HT) increased as well. In vitro testing of sulfide for inhibition of monoamine oxidase (MAO) activity showed the anion to be inhibitory with an IC₅₀ of 39.1±3.6 M. Inhibition of MAO activity ex vivo could be demonstrated at a dose of 100 mg/kg but not at the lower dose of 30 mg/kg NaHS. Inhibition of enzyme activity could not be demonstrated at this lower dose, possibly due to the well known rapid intramitochondrial metabolism of sulfide. Correlation of synaptosomal and mitochondrial sulfide levels with enzyme inhibition data suggests that inhibition of MAO may be an important contributing factor to the mechanism(s) underlying loss of central respiratory drive after fatal intoxication with H₂S.     

Chronic ethanol exposure differentially regulates NOS1 mRNA levels depending on rat brain area

In vitro experiments were performed on brainstem – spinal cord preparations from mouse neonates to compare the noradrenergic regulations of the respiratory network in the control C3H/HeJ strain and the transgenic Tg8 strain which has been created from the C3H/HeJ strain by deletion of the gene encoding monoamine oxidase A (MAOA), the main enzyme for serotonin degradation. In both control and MAOA-deficient strains, we show: (i) that the pontine A5 area exerts a potent inhibitory modulation on the respiratory rhythm generator; (ii) that noradrenaline application induces a tonic phrenic activity; and (iii) that noradrenaline increases the respiratory rhythm. The latter effect is however delayed and weak in the Tg8 strain. Therefore, MAOA-deficiency has only slightly altered the noradrenergic regulations of the respiratory network.     

脑缺血时皮层扩布性抑制与心功能障碍

目的 :研究树 鼠句脑缺血时单胺氧化酶 (MAO)活化在脑缺血时心功能障碍以及扩布性抑制中的可能作用。方法 :采用光化学法诱导树 鼠句血栓性脑缺血 ,测定缺血区及血清MAO活性、多巴胺及去甲肾上腺素 (NA)水平 ,经电镜观察脑及肾上腺的超微结构。记录仪检测心率(HR)、左室收缩压峰值 (LVSP) ,左室瞬间收缩与舒张最大速率 (±dp/dtmax) ,左室舒张末期压力 (LVEDP) ,平均动脉压 (MAP)。结果 :树鼠句脑缺血过程中血清NA先升高 (由 11.60± 0 .73ng/ml升高至18.46± 0 .3 9ng/ml,P <0 .0 1) ,72h后降至 8.3 2± 1.86ng/ml;血清MAO活性逐渐升高 ,达 2 10 .1± 2 6.67U/ml(P <0 .0 1) ,72h降低至对照水平 ;心功能指标 (±dp/dtmax,LVSP ) ,尤其是HR明显降低 ,由3 17.0± 98.0 1beat/min降至 2 3 7.4± 3 1.90beat/min(P <0 .0 1) ,于2 4h恢复至对照水平。结论 :血栓性脑缺血时血清NA水平明显取决于MAO活性的变化 ,后者对脑缺血时心脏舒缩功能可能具有调节作用。