An analysis of the paradoxical effect of morphine on runway speed and food consumption

A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference. Offprint requests to: W.A.CorrigallThe views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation     

Chronic administration of theophylline to rats induces a post-insulin binding defect in adipocyte glucose transport

Summary To determine whether adenosine is involved in long-term regulation of glucose transport in adipose tissue, we have investigated effects of administration of an adenosine receptor antagonist (theophylline) on adipocyte glucose transport. Rats were injected with theophylline (30 mg/kg, dissolved in 0.9% NaCl) daily for 7 days. Controls were injected with saline. The rats were then killed, and epididymal adipocytes were isolated. Insulin-stimulated glucose transport rates were decreased by about 25%–30% in the cells from theophylline-treated rats at all insulin concentrations tested. The half-maximally effective concentration of insulin was not altered (6.5±0.5 and 6.7±0.5 mU/l in control and treated cells respectively), suggesting a post-insulin binding defect. This was confirmed by the finding that ¹²⁵I-insulin binding to the cells was not altered. Adenosine receptor number and affinity (measured on detergent-solubilized adipocyte extracts using ¹²⁵I-hydroxyphenylisopropyl adenosine) was also not changed by theophylline treatment. We conclude that theophylline administration causes decreased glucose transport rates in rat adipocytes at a post-insulin binding level. Thus, chronic adenosine receptor blockade impairs adipocyte glucose transport, suggesting that adenosine is involved in long-term regulation of glucose metabolism in adipose tissue.     

甲基叔丁基醚无铅汽油肾脏毒性的实验研究

目的：了解甲基叔丁基醚（MTBE）无铅汽油对肾脏的毒性及毒作用机制。方法：昆明种小鼠经呼吸道静式染毒，MTBE无铅汽油22．9、11．4及2．3g/m^3每天一次，连续2h，共22d亚急性染毒。日立－7150型全自动生化仪检测血清中尿素氮（BUN）、肌酐（Cr）含量；肾组织均浆中丙二醛（MDA）和超氧化物歧化酶（SOD）含量分别用荧光法，邻苯三酚自氧化固定时间法测定；电镜观察肾皮质区超微结构的变化，结果：22.9g/m^3染毒组雌性小鼠血清中BUN含量与阴性对照组间比较差异有显著性（P＜0．05）；电镜观察到22.9g/m^3染色毒对照组雌雄性小鼠的肾小球基底膜，肾小管细胞线粒体及绒毛均未见显著异常改变。结论：MTBE无铅汽油对肾小球的滤过功能有一定的影响，雌性小鼠可能更为敏感。     

Enhancement of performance by methyl β-carboline-3-carboxylate, in learning and memory tasks

Benzodiazepines are known to induce a profound anterograde amnesia in man. In this report, it is shown that methyl β-carboline-3-carboxylate (β-CCM), an inverse agonist of the benzodiazepine receptor, has the opposite effect; it enhances performance in learning and memory tasks. Three different learning models were used: habituation to a new environment and passive avoidance in mice and imprinting in chicks. The opposite effects of both β-CCM and the benzodiazepine diazepam were blocked by administration of the benzodiazepine receptor antagonist Ro 15-1788, provicling evidence that the benzodiazepine receptor is involved in these effects.     

加杨雄花序的化学成分研究

首次对加杨雄花序了条统从其撮物的石油醚（６０～９０℃）部分,乙酸乙酯部分分离并鉴定了１５个化合物,本语文报道８个黄酮类成分,乔松酮（ｐｉｎｏｓｔｒｏｂｉｎ,１）,高良姜素－３－甲氧基（ｇａ／ｌａｎｇｉｎ ３ ｍｅｔｈｏｘｙ,２）,乔松索（ｐｉｎｏｃｅｒｍｂｉｎ,２）,白杨素（ｃｈｒｙｓｉｎ,４）槲皮素－３,７－二甲氧基（ｑｕｅｒｃｅｔｉｎ０－３,７－ｄｉｍｅｔｈｏｘｙ,５）,鼠李素（ｒｈａｍｍｅｔ     

甲基叔丁基醚的急性毒性研究

为研究国产甲基叔丁基醚（ＭＴＢＥ）的毒性,比较与国外产品的异同,选用大、小鼠及家兔,采用经口、呼吸道及皮肤等染毒途径,同时对国产及进口ＭＴＢＥ的急性毒性进行研究,结果表明：国产及进口ＭＴＢＥ的小鼠经口ＬＤ５０分别为２９４５．２和２９４４．４ｍｇ／ｋｇ,大鼠均为３４３３．６ｍｇ／ｋｇ。小鼠经呼吸道ＬＣ５０分别为７２９８８．３和９９６３０ｍｇ／ｍ３,大鼠为８５３２０和１０３４１０ｍｇ／ｍ３。急性中毒表现均为先兴奋,然后出现粘膜刺激症状,运动失调,活动减少,麻醉,最后死亡。兔经皮染毒仅见脱脂现象,无致炎、致敏或中毒作用。但对兔眼睛有较强致炎作用。结论：国产或进口ＭＴＢＥ的动物经口或经呼吸道急性毒性基本相同,均属低毒物,经皮属微毒物,但对兔眼有明显刺激和致炎作用     

Degradation of methyl and ethyl mercury into inorganic mercury by oxygen free radical-producing systems: Involvement of hydroxyl radical

Degradation of methyl mercury (MeHg) and ethyl Hg (EtHg) with oxygen free radicals was studied in vitro by using three well-known hydroxyl radical (OH)-producing systems, namely Cu²⁺-ascorbate, xanthine oxidase (XOD)-hypoxanthine (HPX)-Fe(III)EDTA and hydrogen peroxide (H₂O₂)-ultraviolet light B. For this purpose, the direct determination method for inorganic Hg was employed. MeHg and EtHg were readily degraded by these three systems, though the amounts of inorganic Hg generated from MeHg were one half to one third those from EtHg. Degradation activity of XOD-HPX-Fe(III)EDTA system was inhibited by Superoxide dismutase, catalase and the OH scavengers and stimulated by H₂O₂. Deletion of the OH formation promoter Fe(III)EDTA from XOD-HPX-Fe(III)EDTA system resulted in the decreased degradation of MeHg and EtHg, which was enhanced by further addition of the iron chelator diethylenetriamine pentaacetic acid. In all these cases, a good correlation was observed between alkyl Hg degradation and deoxyribose oxidation determining OH. By contrast, their degradation appeared to be unrelated to either Superoxide anion production or H₂O₂ production alone. We further confirmed that H₂O₂ (below 2 mM) itself did not cause significant degradation of MeHg and EtHg. These results suggested that OH, but not and H₂O₂, might be the oxygen free radical mainly responsible for the degradation of MeHg and EtHg.     

N-甲基-D-天门冬氨酸受体及其调控的钙内流在大鼠感染性脑损伤中的变化

为探讨Ｎ－甲基－Ｄ－天门冬氨酸（ＮＭＤＡ）受体及其调控的钙内流在感染性脑损伤发病机制中的作用，采用Ｆｕｒａ－２／Ａｍ荧光法检测大鼠大脑皮质突触体内游离钙浓度（［Ｃａ＋＋］ｉ）。结果表明，注射百日咳杆菌组的［Ｃａ＋＋］ｉ较对照组显著增加（Ｐ均＜０．０１），并与注菌时间呈正相关关系（４小时ｖｓ０．５小时和２４小时ｖｓ４小时，Ｐ＜０．０５和＜０．０１）。ＮＭＤＡ受体的非竞争性拮抗剂ＭＫ－８０１预处理组（ＭＢＰ）的［Ｃａ＋＋］ｉ、脑含水量和伊文思蓝含量均较注菌组显著减少（Ｆ值分别为７２．２５、１６．８９、１４．３６，Ｐ＜０．０１和＜０．０５），并以２４小时［Ｃａ＋＋］ｉ减少最为明显（Ｐ＜０．０１）。提示ＮＭＤＡ受体调控的神经元内钙超载在感染性脑损伤、尤其在迟发性脑损伤的发病机制中起着重要作用。     

氯乙酸甲酯亚慢性染毒大鼠睾丸组织和血清睾酮水平变化

目的研究氯乙酸甲酯亚慢性染毒大鼠睾丸功能和组织学变化。方法将55只雄性大鼠随机分成5组,4个剂量组分别给予4.3、8.6、17.2和34.4mg/kg的氯乙酸甲酯,对照组给予生理盐水共13周,观察睾丸和附睾组织形态学的变化,检测精子活力、精子计数以及精子畸形率,血清睾酮水平和睾丸细胞的凋亡率。结果高剂量染毒组睾丸脏器系数、血清睾酮水平、睾丸细胞凋亡率[0.85±0.05、(5.93±2.75)μg/L、(18.22±7.03)%]与对照组[0.80±0.09、(14.70±8.04)μg/L、(6.40±4.51)%]之间差异有显著性(P<0.05)。结论最高剂量氯乙酸甲酯处理大鼠睾丸和血清睾酮水平有变化。