Alcohol dependence and opiate dependence: lack of relationship in mice

According to a recently proposed hypothesis, physical dependence upon alcohol is due to the formation of an endogenous opiate. We tested the hypothesis by determining whether or not ethanol-dependent mice would show typical opiate-dependent behavior (withdrawal jumping syndrome) when challenged with the opiate antagonist naloxone. Our results do not support the hypothesis.     

Narcotic drugs: effects on the serotonin biosynthetic systems of the brain

The effects of short- and long-term administration of morphine on the activity of two measurable forms of rat brain tryptophan hydroxylase were studied. Morphine administration produced an immediate decrease and a longterm increase in the nerve ending (particulate) enzyme activity but did not change the cell body (soluble) enzyme activity. Cocaine administration demnonstrated a short-term decrcease in measurable nerve eniding enzyme activity that was due to the inhibition of the high affinity uptake (the Michaelis constant, K(m) is 10-(5) molar) of trytophan, the serotonin precursor. Cocaine did not aflect the low affinity uptake K(m) = 10-(5) molar) of tryptophan. Both the uptake of the precursor and the enizymiie activity appeared to be drug-sensitive regullatory processes in the biosynthlesis of serotonin.     

Benzodiazepines: anxiety-reducing activity by reduction of serotonin turnover in the brain

The anxiety-reducing effects of minor tranquilizers in the rat conflict test were mimicked by serotonin antagonists and by p-chlorophenylalanine, an inhibitor of serotonin synthesis; the depressant effects of the minor tranquilizers were mimicked by norepinephrine antagonists. Intraventricular injections of serotonin led to a suppression of behavior, and also antagonized the anxiety-reducing action of benzodiazeprines. Intraventricular injections of norepinephrine led to a release of punished behavior from suppression, and also antagonized the depressant action of benzodiazepines. The anxiety-reducing activity, and the decrease in serotonin turnover induced by benzodiazepines, were maintained over repeated doses, whereas depressant activity, and the decrease induced in norepinephrine turnover, both rapidly underwent tolerance. Tranquilizers may exert their anxiety-reducing effects by a reduction of serotonin activity in a behaviorally suppressive punishment system, and they may exert their depressant effects by a reduction of norepinephrine activity in a behaviorally facilitatory reward system.     

Persistent increase in brain serotonin turnover after chronic administration of LSD in the rat

Lysergic acid diethylamide at doses of 20 micrograms per kilogram per day was administered orally to rats for I month. Eighteen hours after the final dose a 25 to 30 percent increase in the synthesis and turnover of serotonin was noted, as well as a moderate but significant increase in the concentration of tryptophan (18 percent) and serotonin (13 percent) in the brain.     

Morphine tolerance, physical dependence, and synthesis of brain 5-hydroxytryptamine

Tolerance and physical dependence development to morphine in mice can be prevented by concomitant administration of cycloheximide. The fact that the rate of synthesis of brain 5-hydroxytryptamine (5HT) increases with tolerance to morphine suggests that the protein involved may be associated with 5HT synthesis. Inhibition of this synthesis with p-chlorophenylalanine markedly decreases tolerance and physical dependence development to morphine.     

Autoradiographic imaging of phosphoinositide turnover in the brain

With [3H]cytidine as a precursor, phosphoinositide turnover can be localized in brain slices by selective autoradiography of the product [3H]cytidine diphosphate diacylglycerol, which is membrane-bound. In the cerebellum, glutamatergic stimulation elicits an increase of phosphoinositide turnover only in Purkinje cells and the molecular layer. In the hippocampus, both glutamatergic and muscarinic cholinergic stimulation increase phosphoinositide turnover, but with distinct localizations. Cholinergic stimulation affects CA1, CA3, CA4, and subiculum, whereas glutamatergic effects are restricted to the subiculum and CA3. Imaging phosphoinositide turnover in brain slices, which are amenable to electrophysiologic studies, will permit a dynamic localized analysis of regulation of this second messenger in response to synaptic stimulation of specific neuronal pathways.     

Alcohol preference in the rat: reduction following depletion of brain serotonin

Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p-chlorophenylalanine was administered, but the rats' rejection of alcohol was even more marked after the drug was discontinued. Oral administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as alpha-methyl-p-tyrosine was terminated.     

Monosodium glutamate: lack of effects on brain and reproductive function in rats

Monosodium glutamate was injected subcutaneously in infant rats of both sexes. The lateral preoptic and arcuate nuclei and median eminence were examined by light and electron microscopy for possible monosodium glutamate effects. As adults, treated animals showed no adverse monosodium glutamate effects on the reproductive system and neural morphology.     

Sleep patterns of the monkey and brain serotonin concentration: effect of p-chlorophenylalanine

The amount of time that monkeys (Macaca mulatta) slept was reduced after they were given p-chlorophenylalanine, a selective depletor of serotonin in animal tissues. The time spent in the rapid eye movement stage of sleep was unchanged, but the time in other sleep stages decreased. Seven regions of the brain had a 31 to 46 percent decrease in serotonin content; the concentration of cerebellar serotonin increased by 44 percent.     

Norepinephrine pools in rat brain: differences in turnover rates and pathways of metabolism

The rate of disappearance of intracisternally administered [(3)H]norepinephrine from rat brain gradually declines as a multiphasic exponential function of time. Conversion to [(3)H]normetanephrine accounts for a larger fraction of the [(3)H]norepinephrine released in the brain shortly after its intracisternal injection than that released at later times. Pools of norepinephrine in the brain thus appear to differ in their turnover rates and pathways of metabolism. The pool of norepinephrine with a rapid rate of turnover and an appreciable conversion to normetanephrine, identified by the techniques reported here, may correspond to a pool of newly synthesized norepinephrine in the brain.     

Effects of phenylalanine diet on brain serotonin in the rat

Hooded rats fed diets rich in phenylalanine showed poorer performance on the Hebb-Williams maze than controls, as well as decreased brain serotonin levels. There did not appear to be a causal relationship between these findings, and the findings do not appear to be attributable either to a generalized behavioral defect or to inadequate dietary intake.     

谷子MYB转录因子家族与抗旱关系的研究

[目的]MYB蛋白家族是一类含有MYB保守结构域的转录因子,广泛参与调控植物生长发育及抗逆等多种生理反应。为探究抗旱作物谷子的抗旱性与MYB转录因子家族基因关系,从而为谷子特有抗旱基因资源的发掘及谷子抗旱分子机制的研究提供参考。[方法]本研究以抗旱品种勾勾母鸡咀(GG)和干旱敏感品种晋汾16(JF)为研究对象,在苗期PEG处理条件下,取叶片进行转录组测序,进而对有差异表达的MYB转录因子家族基因进行生物信息学分析。[结果]研究表明,26个MYB转录因子基因在GG和JF两个谷子品种中表现出较为明显的表达差异;且对应启动子区域的抗旱相关调控元件也呈现出差异的组成与分布;抗旱品种GG中明显上调的3个MYB调控基因(Si034363m、Si003539m、Si030711m)与拟南芥中主要参与抗逆的MYB转录因子存在较近亲缘关系。[结论]基于对谷子MYB转录因子的研究,推测26个表达差异的MYB类转录因子基因可作为谷子抗旱的重要候选基因,可为后续谷子抗旱分子机制的研究提供理论依据。     

谷子硒结合蛋白基因及其与抗旱性的关系

[目的]土壤与肥料中的硒元素进入植物体后,与植物中的蛋白质和活性有机成分结合成为植物有机硒,即植物硒结合蛋白。本研究以硒结合蛋白结构和功能为基础,探索其与谷子抗旱的关系。[方法]以谷子耐旱品种勾勾母鸡咀(GG)和干旱敏感品种晋汾16(JF16)为试材,以转录组中硒结合蛋白基因家族中10个基因为对象,利用生物信息学分析其基因组基本信息、基因间亲缘关系及启动子顺式元件,并对Seita.4G100300基因进行表达水平分析。[结果]发现谷子硒结合蛋白基因家族中基因启动子上游1 500bp的调控元件具有响应胁迫的多种功能(ABA、Ethylene、GA、MeJA、Light、MYB、SA、热和低温等);经过干旱处理,Seita.4G100300基因在GG和JF16中表达水平均增加,且其在耐干旱品种GG中表达水平的增幅显著大于干旱敏感品种JF16。[结论]谷子硒结合蛋白基因家族在氨基酸序列和表达模式方面具有较为丰富的多样性。本研究有助于我们理解硒结合蛋白的结构和功能,为进一步研究硒结合蛋白与植物抗逆性关系提供理论依据。     

Evoked release of norepinephrine and serotonin from brain slices: inhibitoon by lithium

Slices of mammalian brain accumulate H(3)-norepinephrine and H(3)-serotonin when incubated in a physiologic medium containing these tritiated monoamines. When these tissues are subjected to mild electrical stimulation of short duration, which is associated with depolarization of nerve membranes, a striking increase in the rate of efflux of the exogenous labeled monoamines occurs. Stimulation-induced release of both labeled monoamines is diminished by the presence of lithium ions in the perfusing medium; related monovalent cations had no such effect. Evoked release from slices of brain from animals treated intraperitoneally with lithium chloride for 3 days was also reduced.     

Neocortical transplants in the mammalian brain lack a blood-brain barrier to macromolecules

In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.     

Norepinephrine turnover and metabolism in rat brain after long-term administration of imipramine

The rate of disappearance of intracisternally administered tritiated norepinephrine from rat brain is decreased after a single dose of the tricyclic antidepressant imipramine. During long-term administration of imipramine, however, the rate of disappearance of tritiated norepinephrine from brain gradually increases, and there is a concurrent decrease in the content of endogenous norepinephrine in brain. These findings may help to explain why antidepressant effects are observed clinically only after long-termn treatment with imipramine.     

Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801.

The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.