吗啡依赖和戒断对大鼠杏仁核神经甾体和氨基酸递质水平的影响

目的研究吗啡依赖和戒断时大鼠杏仁核中神经甾体和氨基酸递质水平的变化。方法连续7天给予大鼠盐酸吗啡建立吗啡依赖模型。使用纳洛酮(2mg/kg)催促戒断,观察戒断症状并进行评分。将大鼠断头处死后,剥离大脑并分离出杏仁核,用液-液萃取和固相萃取法提取游离型和结合型神经甾体。神经甾体(包括脱氢表雄酮、孕烯醇酮、别孕烯醇酮、脱氢表雄酮硫酸酯和孕烯醇酮硫酸酯)的含量使用高效液相色谱-质谱法测定。甘氨酸、谷氨酸和γ-氨基丁酸的含量采用柱前OPA衍生-电化学检测-高效液相色谱法测定。结果与盐水对照组相比,吗啡依赖大鼠杏仁核中的脱氢表雄酮水平降低33 %(P<0·01)。与戒断对照组比较,吗啡戒断大鼠杏仁核中的孕烯醇酮和别孕烯醇酮水平分别升高45 %和42 %(P<0·05) ,γ-氨基丁酸水平降低18 %(P<0·01)。与吗啡依赖组比较,吗啡戒断组大鼠杏仁核中的孕烯醇酮和孕烯醇酮硫酸酯水平分别升高60 %和40 %(P<0·05) ,甘氨酸水平降低14 %(P<0·05)。结论吗啡依赖大鼠杏仁核中的脱氢表雄酮可能参与吗啡依赖的形成而与吗啡戒断症状的表达无关。其他神经甾体(包括孕烯醇酮、别孕烯醇酮和孕烯醇酮硫酸酯)则可能参与吗啡的戒断而与依赖的形成无关。纳洛酮催促戒断时,大鼠杏仁核中抑制性氨基酸递质的合成和释放受到抑制。表明大鼠杏仁核中的各种神经甾体和氨基酸递质在吗啡依赖和戒断时发生了不同的变化。     

Development of neurochemical separation of ON and OFF channels at retinal ganglion cells

Anatomical and physiological segregation of neurons into ON (brightening detector) and OFF (darkening detector) channels in the retina and subsequent visual system ensure the high sensitivity required for contrast detection and spatial discrimination. This segregation is finest at the visual axis. Neurochemically, ON and OFF ganglion cells at the visual axis seem to be distinguished by different inhibitory transmitters but not excitatory transmitters. Microiontophoretic studies of inhibitory transmitters on the retinal ganglion cells in kittens and adult cats suggest that this neurochemical distinction is poor in immature ganglion cells at the visual axis. Initially both ON and OFF cells seem to be supplied by GABAergic, glycinergic, and catecholaminergic amacrine cells, but in adults, ON cells remain supplied only by GABAergic amacrines, while OFF cells are supplied by glycinergic amacrines. Postnatal elimination of multiple inputs and strengthening of the appropriate inputs, as seen in the central nervous system, also seem to occur at the retinal neurotransmitter synapses during development.     

D-Cycloserine enhances social behaviour in individually-housed mice in the resident-intruder test

D-Cycloserine (DCS) has been reported to affect the central nervous system in man. To investigate whether the compound produces specific behavioural effects, DCS was administered to male mice in a resident-intruder situation and the behaviour of the interacting mice assessed using ethological analysis. Resident mice given DCS (32.0–320.0 mg/kg PO, 60 min before testing) showed dose-dependent increases in social investigation, smaller increases in sexual behaviour and decreased aggressiveness. Defensive and flight behaviour were not affected. Intruder mice showed slight increases in sexual behaviour that were not dose-dependent, and small increases in social investigation. The increases in social investigation induced by DCS (320.0 mg/kg) in resident mice were not reversible with R-HA 966 (32.0 mg/kg IP, 30 min before testing), a blocker of the strychnine-insensitive glycine modulatory site associated with theN-methyl-D-aspartate receptor, but were blocked by the GABA antagonist bicuculline (0.56 mg/kg IP, 5 min before testing). The small DCS-induced increase in sexual behaviour in residents was reversed by R-HA 966. Within the parameters of the resident-intruder situation, DCS exerts socio-sexual behaviour-enhancing effects which are dependent upon the role of the interactant, and which are mediated by an action upon multiple substrates. DCS may be regarded as another example of a sociotropic (approach-promoting) agent.Some of these results have been presented at the 1^st International Congress on Hormones, Brain and Neuropsychopharmacology, Rodos, Greece, September 12–17, 1993     

Synapses of cone horizontal cell axons in goldfish retina

The axon terminals of cone horizontal cells in the goldfish retina form typical chemical synaptic contacts in the middle of the inner nuclear layer. Approximately 60% of the identified postsynaptic elements were perikarya, axons and dendrites of bipolar cells. The other identified postsynaptic elements were perikarya and processes of interplexiform cells. We propose that the horizontal cell axon terminal contribute to the antagonistic surround responses of the bipolar cells and that they modulate inputs to the outer plexiform layer conveyed by interplexiform cells. Output synapses from horizontal cell axons to unidentified neuronal processes as well as occasional input synapses to the axons from interplexiform cell processes and unidentified perikarya were also observed in the same region of the inner nuclear layer.     

Modulation of dopamine function by glycine in the nucleus accumbens of the brain of the rat

The effects of glycine on the phasic changes in locomotor activity in the rat, caused by a persistent infusion of dopamine (DA) into the nucleus accumbens (ACB) were investigated. Dopamine (25 μg/24 hr), infused into the nucleus accumbens for 13 days, caused hyperactivity, with two peaks occurring on days 3–4 and 9–11. Glycine (12.5 or 25 μg/24 hr) infused into the nucleus accumbens on its own did not alter the locomotor activity, yet when infused at the same time as DA (25 μg/24 hr), glycine (12.5 or 25 μg/24 hr) inhibited the development of the first peak of hyperactivity induced by DA, with no effect on the second peak. A larger dose of glycine (50 μg/24 hr), infused alone, significantly increased locomotor activity, and a combination of this dose with DA (25 μg/24 hr), led to a temporal shift in the response to DA such that the first peak of hyperactivity was delayed to “fuse” with the second peak. The locomotor response to a threshold dose of DA (6.25 μg/24 hr) plus glycine (50 μg/24 hr) was no greater than could be accounted for by the hyperactivity response to glycine alone (50 μg/24 hr). Strychnine (10 μg/24 hr), infused into the nucleus accumbens, produced no alteration in locomotor activity. Similarly, when infused together with DA (25 μg/24 hr), strychnine (10 μg/24 hr) caused no significant alteration in the phasic hyperactivity induced by DA. However, strychnine (10 μg/24 hr), infused together with DA and glycine (25 and 12.5 μg/24 hr respectively), prevented the inhibition by glycine of the first peak of hyperactivity induced by DA. The results indicate that while glycine may not normally exert a tonic modulatory influence on those mechanisms in the nucleus accumbens which regulate locomotor activity, when applied exogenously glycine can partially moderate the locomotor response to DA, through an action on strychnine-sensitive receptors.     

Conformation of glycyl residues in globular proteins

Glycine is unique among the amino acids in view of its symmetric nature. While the overall distribution of glycyl residues in the (φ, ø) plane is near-symmetric, there can be certain preferences for the individual conformations. An analysis of the observed glycyl conformations in 70 proteins has been carried out to find the influence of residues adjoining the glycyl residues. For this purpose, the (φ, ø) plane has been divided into two regions: (a) the region in which φ is negative and (b) the region in which φ is positive. The analysis is done in terms of the number of conformations occurring in these regions. It has been found that while the overall percentage distribution of glycyl residues between the positive and the negative φ regions is 54:46, the distribution shows asymmetry when the examples are sorted out in terms of X-Gly and Gly-Y doublets. The asymmetry becomes more prominent when the data are sorted out into triplets X-Gly-Y. Using the available information, it has been possible to designate 25 triplets as P-predominant and 19 as N-predominant. An examination of P-predominant triplets for possible occurrence in β-bends having one of the conformations in the positive φ region shows that only 25% are of this nature. Thus, the P-preference of P-predominant triplets is not an outcome of the bend formation alone and must be an inherent property of these triplets.     

三种氨基酸对兔血浆皮质酮浓度的影响

侧脑室注射甘氨酸使健康家兔和烧伤家兔血浆皮质酮浓度降低;注射L—谷氨酸和L—天冬氨酸使健康家兔血浆皮质酮浓度升高,但不能使烧伤后升高的血浆皮质酮浓度发生改变。提示这三种氨基酸作为神经递质参与下丘脑—垂体—肾上腺皮质轴的调控。烧伤刺激通过下丘脑引起内分泌紊乱,这种紊乱与L—谷氨酸和L—天冬氨酸失控有关。     

甘氨酸螯合铁的合成工艺

以氯化亚铁和甘氨酸为原料,研究了甘氨酸螯合铁的合成工艺条件.结果表明,pH值、配位比以及抗氧化剂用量对产品组成和得率有很大影响.确定了螯合的最适条件为:pH值为5.5、配位比为4∶1.采用有机溶剂萃取法,使甘氨酸螯合铁在无水乙醇中以沉淀的方式析出,实现甘氨酸螯合铁与无机铁的分离.讨论了萃取时有机溶剂用量对产品得率的影响,在无水乙醇与滤液的体积比为9∶1时,亚铁得率最高.     

Transmitter Release Associated with Long-term Synaptic Depression in Rat Corticostriatal Slices

Using a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long-term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s duration, 20 s intervals) used to induce LTD caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.     

Use of a synthetic peptide-based elisa for the diagnosis of infectious mononucleosis and other diseases

A simple enzyme immunoassay has been developed based on measuring antibodies to synthetic peptides corresponding to sequences in the Epstein-Barr nuclear antigen (EBNA). This assay, which is reproducible, quantitative, and simple to perform and interpret, can be an effective tool to aid in the diagnosis of infectious mononucleosis and nasopharyngeal carcinoma.