Brain glycine and aggressive behavior.

Intraperitoneal glycine reduced aggressiveness caused by water deprivation or forebrain septal lesion in the rat. Nalorphine and mephenesin, drugs previously shown to elevate central glycine levels, acted in the same way as systemically administered glycine. In mice made aggressive by prolonged isolation, glycine and mephenesin acted as tranquilizers, but nalorphine failed to act. Aggressiveness in mice, induced by L-dopa or clonidine was enhanced by nalorphine and mephenesin, but was left unaffected by systemically administered glycine. Behavioral effects of glycine extend to other forms of excitation.     

Pharmacological studies on facial motoneurones in the rat

Experiments were performed on 39 male albino rats anaesthetized with pentobarbitone sodium and paralyzed with gallamine triethiodide. Facial motoneurones consistently showed a progressive alteration of spike shape and decrease in spike firing frequency during the continuous microelectrophoretic application of the excitant amino acids D,L-homocysteate, L-glutamate, L-aspartate, and kainate, but infrequently during that of N-methyl-D-asparate. The relative potencies of these excitants on facial motoneurones are reported. The potential usefulness of N-methyl-D-aspartate to produce amino acid-evoked motoneurone action potentials is discussed.The microelectrophoretically-applied depressant amino acid antagonist strychnine selectively and reversibly blocked the depressant effects of glycine on facial motoneurones. The depression of amino acid-induced firing of facial motoneurones by stimuli to the lingual or glossopharyngeal nerves were reversibly antagonized by microelectrophoretically applied strychnine but not by bicuculine.     

Connexions between retinal neurons with identified neurotransmitters

Dopaminergic and indoleamine accumulating neurons can be demonstrated both in the light and the electron microscopes. Considerable differences have been found between different animal species. There are two types of dopaminergic neurons, the interamacrine cells and the interplexiform cells. The interamacrine cells contact only other amacrine cells. They receive synapses from other amacrine cells which are likely to operate with, e.g. GABA or glycine as neurotransmitter. The dopamine turnover in the dopaminergic interamacrine cells is very rapidly activated by light. Dopaminergic interplexiform neurons are known only in teleost fish and New World monkeys. They have approximately the same contacts in the inner plexiform layer as the interamacrine cells, but, in addition, send processes to the outer plexiform layer and there contact both horizontal cells and bipolar cells. The function of the dopaminergic neurons has not been determined. The indoleamine accumulating amacrine neurons are in Cebus monkeys, cats and rabbits contacted by bipolar cells in dyads and form reciprocal synapses with them. They are also contacted by amacrine cells and make synapses on other with them. They are also contacted by amacrine cells and make synapses on other amacrine cells and on ganglion cells. The contacts are different in teleost fish, where the indoleamine accumulating cells mainly contact other amacrine cells only. The transmitter of the indoleamine accumulating neurons is debated in mammals but is most likely 5-hydroxytryptamine in other vertebrates.     

Neurochemical correlates of behavior: levels of amino acids in four areas of the brain of the rat during drug-induced behavioral excitation.

The levels of GABA, aspartate, glutamate, glycine and alanine were determined in 4 specific brain areas (telencephalon, diencephalon-mesencephalon cerebellum and pons-medulla oblongata) of rats killed during a period of drug-induced behavioral excitation. Behavioral excitation was obtained in adult, male Wistar rats working on a Sidman shock-avoidance schedule following administration of 2 mg/kg tetrabenazine (TBZ) 18 hr after iproniazid (50 mg/kg) pretreatment. When compared to trained animals (working on the avoidance schedule but receiving no drugs), the excited rats had increased levels of GABA in the telencephalon and diencephalon-mesencephalon, decreased levels of aspartate in all 4 brain areas, and a lower content of glycine in the pons-medulla region. The changes in the levels of aspartate in all areas of the brain, GABA in the diencephalon-mesencephalon, and glycine in the pons-medulla were significantly correlated (p less than 0.01) with the degree of excitation. It was observed that avoidance training alone produced increases in the levels of four amino acids: aspartate in telencephalon and cerebellum, GABA in cerebellum, and glycine and glutamate in the pons-medulla. The injection of iproniazid alone or iproniazid followed by TBZ into naive animals had little effect on the levels of the five amino acids. The data are discussed in terms of aspartate and GABA interacting as neurotransmitters with cholinergic and catecholaminergic and/or serotonergic neurons to produced the behavioral excitation.     

Neuroactive amino acids in the area postrema

Summary The localization of five neuroactive amino acids in the rat area postrema was studied by postembedding immunocytochemistry in semithin and ultrathin sections. Antisera to GABA, glycine, glutamate and aspartate produced labelling of cells that were identified as neurons in the electron microscope. GABA-like and glycine-like immunoreactivities occurred in about 20% and 60% of the neurons, respectively, and a minor proportion of the cells displayed both immunoreactivities, suggesting a cellular colocalization of GABA and glycine. Immunoreactivities for glutamate and aspartate were found in a large majority of the neurons, including most of the cells that were positive for GABA and/or glycine. Taurine immunoreactivity was highly concentrated in a few small cells with ultrastructural features typical of microglial cells, and in processes that were probably derived from these. Taurine also appeared to be abundant in cells confined to the perivascular space. The electron microscopic, immunogold analysis of the neuropil revealed numerous nerve terminals that were enriched in GABA or glutamate immunoreactivity, compatible with a transmitter role of these amino acids. Glycine immunolabelling was found preferentially in post-synaptic elements, suggesting that the glycine-containing cells lack locally ramifying axon collaterals, and that they mainly project outside the area postrema. Aspartate immunolabelling was also generally low in axon terminals. This is similar to the situation in several other brain areas and could indicate that the latter amino acid primarily serves metabolic functions in the area postrema.     

Modulation of GABAA and glycine receptors by chlormethiazole

The influence of chlormethiazole, on currents evoked by γ-aminobutyric acid (GABA) and glycine, was investigated under voltage-clamp conditions, in bovine chromaffin cells and murine spinal neurones, respectively. Chlormethiazole (30 and 100 μM) dose dependently potentiated currents activated by either inhibitory neurotransmitter. The potentiation of the GABA-evoked response occurred without altering the reversal potential and was not influenced by the benzodiazepine receptor antagonist Ro 15-1788 (300 nM). GABA-gated channels, recorded from outside-out membrane patches, showed increased probability of being in the conducting state in the presence of chlormethiazole. High concentrations of chlormethiazole (3 mM) activated bicuculline (1 μM)-sensitive whole-cell currents with a reversal potential similar to the chloride equilibrium potential. Chlormethiazole potentiates GABA- and glycine-activated currents and at higher doses, directly activates the GABA_A receptor.     

甘氨酸对高果糖饮食诱导的大鼠胰岛素抵抗及认知功能损害的影响

目的: 探讨肠源性内毒素血症(IETM)在长期高果糖饮食诱导的大鼠胰岛素抵抗(IR)及认知功能损害中的作用,及甘氨酸对其的保护机制。方法: 模型组大鼠以8%果糖水喂养,干预组给予8%果糖+1%甘氨酸水喂养。每月检测体重及收缩压。8个月后,检测血糖、血脂、糖耐量及血浆内毒素(LPS)变化;ELISA法检测血浆胰岛素、血浆及皮层促炎因子水平;计算胰岛素抵抗指数(HOMA-IR);Western blotting测定皮层胰岛素受体信号转导蛋白的表达;应用Morris水迷宫测试大鼠认知功能。结果: 模型组在第3月~第6月体重增长明显,第3月后收缩压明显升高;甘氨酸在第4月和第6月显著降低模型组体重增长,第4~第6月降低收缩压的升高。甘氨酸部分改善模型组血脂和糖耐量异常,降低血浆LPS、血浆胰岛素、HOMA-IR、血浆和皮层促炎因子水平。此外,甘氨酸还明显改善模型组皮层胰岛素信号转导蛋白的异常表达及认知功能损害。结论: 长期高果糖饮食诱导大鼠发生外周及中枢的IR,同时伴有IETM和轻度炎症;甘氨酸通过减轻IETM改善高果糖饮食诱导的IR和认知功能损害。     

Glycine Receptors Contribute to Hypnosis Induced by Ethanol

Background:  Glycine is a major inhibitory neurotransmitter in the adult central nervous system (CNS), and its receptors (GlyRs) are well known for their effects in the spinal cord and the lower brainstem. Accumulating evidence indicates that GlyRs are more widely distributed in the CNS, including many supraspinal regions. Previous in vitro studies have demonstrated that ethanol potentiates the function of these brain GlyRs, yet the behavioral role of the brain GlyRs has not been well explored.
Methods:  Experiments were conducted in rats. The loss of righting reflex (LORR) was used as a marker of the hypnotic state. We compared the LORR induced by systematic administration of ethanol and of ketamine in the absence and presence of the selective glycine receptor antagonist strychnine. Ketamine is a general anesthetic that does not affect GlyRs.
Results:  Systemically administered (by intraperitoneal injection) ethanol and ketamine dose-dependently induced LORR in rats. Furthermore, systemically administered (by subcutaneous injection) strychnine dose-dependently reduced the percentage of rats exhibiting LORR induced by ethanol, increased the onset time, and decreased the duration of LORR. Strychnine had no effect, however, on the LORR induced by ketamine.
Conclusions:  Given that hypnosis is caused by neuronal depression in upper brain areas, we therefore conclude that brain GlyRs contribute at least in part to the hypnosis induced by ethanol.     

The Glycine Reuptake Inhibitor Org 25935 Interacts With Basal and Ethanol-Induced Dopamine Release in Rat Nucleus Accumbens

Background:  The mesolimbic dopamine (DA) projection from the ventral tegmental area to nucleus accumbens (nAc), a central part of the reward system, is activated by ethanol (EtOH) and other drugs of abuse. We have previously demonstrated that the glycine receptor in the nAc and its amino acid agonists may be implicated in the DA activation and reinforcing properties of EtOH. We have also reported that the glycine transporter 1 inhibitor, Org 25935, produces a robust and dose-dependent decrease in EtOH consumption in Wistar rats. The present study explores the interaction between EtOH and Org 25935 with respect to DA levels in the rat nAc.
Methods:  The effects of Org 25935 (6 mg/kg, i.p.) and/or EtOH (2.5 g/kg, i.p.) on accumbal DA levels were examined by means of in vivo microdialysis (coupled to HPLC-ED) in freely moving male Wistar rats. The effect of Org 25935 on accumbal glycine output was also investigated.
Results:  Systemic Org 25935 increased DA output in a subpopulation of rats (52% in Experiment 1 and 38% in Experiment 2 ). In Experiment 2 , EtOH produced a significant increase in DA levels in vehicles (35%) and in Org 25935 nonresponders (19%), whereas EtOH did not further increase the DA level in rats responding to Org 25935 (2%). The same dose of Org 25935 increased glycine levels by 87% in nAc.
Conclusions:  This study demonstrates that Org 25935, probably via increased glycine levels, (i) counteracts EtOH-induced increases of accumbal DA levels and (ii) increases basal DA levels in a subpopulation of rats. The results are in line with previous findings and it is suggested that the effects observed involve interference with accumbal GlyRs and are related to the alcohol consumption modulating effect of Org 25935.     

Immunocytochemical study of glycine receptors in the retina of the frog Xenopus laevis

The expression of glycine receptors in the retina of clawed frog, Xenopus laevis was studied immunocytochemically. Glycine receptors (GlyRs), as revealed by means of several different antibodies, were mainly distributed in the inner (IPL) and the outer plexiform layers. Their composition was determined to include α2 and α3 subunits. Typical punctate appearance and specific lamination in the IPL were seen with each of the antibodies directed against the different GlyRs’ subunits. A notion for diversity of the glycine receptors was put forward, according to which the α2 and α3 subunits are located in different subtypes of glycine synapses.