Attenuation of ethanol tolerance by a novel stimulus

A Pavlovian conditioning model of tolerance emphasizes that an association between predrug cues and the systemic effects of the drug contributes to tolerance. On the basis of this model, established tolerance should be attenuated by external inhibition, i.e., by presentation of a novel, extraneous stimulus. This prediction was evaluated in the present experiment. Rats that were so tolerant to the hypothermic effect of ethanol that they evidenced no drug-induced decrease in temperature were presented with a bright strobe light following ethanol administration. The light precipitated a large decrease in temperature in these rats. These results provide further evidence that tolerance to the hypothermic effect of ethanol is, in part, mediated by learning.     

The effects of ethanol,estrogen, and hexachlorobenzene on the activities of hepatic δ-aminolevulinate synthetase, δ-aminolevulinate dehydratase,and uroporphyrinogen decarboxylase in male rats

To determine if clinically observed disorders in heme biosynthetic enzymes, known as sporadic porphyria cutanea tarda (PCT), could be reproduced in experimental animals, male Fischer rats were treated with ethanol, estrogen and hexachlorobenzene (HCB). A series of heme biosynthetic enzymes were assayed. In the rats given free access to 8% ethanol-drinking water for 15 weeks, -aminolevulinate (ALA) dehydratase was significantly reduced in erythrocytes. In the liver, ALA synthetase and uroporphyrinogen (UROgen) decarboxylase activities remained unchanged. In bone marrow cells, these activities did not change markedly. In the rats treated with estrogen (1 mg estrioltripropionate /rat/week, IM), no body weight gain was observed during the treatment for 15 weeks and urinary ALA excretion increased to 1.7 fold over normal level. In the liver, a significant increase was observed in the activity of ALA dehydratase, but other enzymes remained within the normal level. In bone marrow cells and erythrocytes, ALA dehydratase was also increased. ALA synthetase increased only in bone marrow cells to 2.1 times higher than the control level. In rats fed 0.3% HCB-diet for 8 weeks, urinary excretion of ALA, coproporphyrin and uroporphyrin increased to 2.4, 3.3 and 3.8 times higher than the controls, respectively. In the liver, an increase was observed in ALA synthetase, while a decrease was observed in ALA dehydratase and UROgen decarboxylase. In bone marrow cells and erythrocytes, ALA dehydratase was reduced and activities of other enzymes did not show any changes.These results indicate that alcohol, estrogen and HCB do not produce phenomena similar to those observed clinically in PCT.     

Effects of ethanol on murine aggression assessed by biting of an inanimate target

The effects of acutely administered ethanol (0, 0.5, 1.0 and 2.0 g/kg, IP) were studied in a tube-restraint/target biting model of aggressive responding using naive group-and individually-housed male Swiss mice. Behavioural measures were the latency to the first bite and the biting frequency. In saline-injected control animals, the levels of responding were significantly higher in group-housed than isolated mice. Animals given alcohol exhibited a dose-dependent suppression of biting frequency, and an increase in biting latency. Mice experienced in the tube-testing situation showed reduced baseline levels of biting, but alcohol produced similar effects to those in naive mice. There was no evidence of a biphasic action of alcohol.     

甲醇沉淀-高效液相色谱法同时测定奶茶中5种添加剂

目的建立甲醇沉淀-高效液相色谱同时测定奶茶中安赛蜜、苯甲酸、糖精钠、山梨酸和咖啡因的方法。方法样品加甲醇沉淀旋涡混合提取后,离心分离,取上清液,过0.22μm滤膜,高效液相色谱检测。色谱条件:使用Agilent Poroshell 120 EC-C₁₈(3 mm×150 mm,2.7μm)色谱柱,以甲醇和0.02 mol/L乙酸铵溶液为流动相,梯度洗脱,流速为1.0 ml/min,柱温为35℃,检测波长为240 nm。结果 5种添加剂在1.0μg/ml~50.0μg/ml线性良好,r>0.999 9,方法检出限为0.002 g/kg~0.005 g/kg,测定限为0.006 g/kg~0.015 g/kg。对饮料进行高、中、低3个浓度水平测定,回收率为93.36%~104.5%,相对标准偏差(RSD)为1.0%~3.4%。结论本方法样品预处理简单、分离效果好、准确度高,适用于奶茶中安赛蜜、苯甲酸、糖精钠、山梨酸和咖啡因的同时检测。     

Distinctions among sedative,disinhibitory, and ataxic properties of ethanol in inbred and selectively bred mice

Three different domains of behavioral action of ethanol (ETOH) were examined in a battery of seven inbred strains and in the selectively bred Long-Sleep (LS) and Short-Sleep (SS) mice. Sedative effects were examined with the loss of the righting reflex test at 3.8 g/kg. The variation among inbred strains was only half the size of the difference between LS and SS mice which were selectively bred for extremes in this phenotype; such a result is expected for phenotypes controlled polygenically. Blood ETOH levels at waking from the narcosis also showed a range of differences among the inbred strains that was less than the LS/SS difference. Ataxia was measured with the grid test, and the inbred strains fell into two groups, resembling the highly ataxic LS line, and the less ataxic SS line. Biphasic effects of ETOH on locomotor activity were strongly genotype dependent. Variation in degree of activation/disinhibition produced by doses up to 1.5 g/kg (IP) ranged from no activation, in the C57BL/6Abg strain, to a stimulation effect in the MOLD/RkAbg strain which was larger than that seen for SS mice. The patterns of strain differences for both ataxia and activation were highly different from the duration of loss of righting reflex measure, suggesting multiple independent genetically based sensitivities to ETOH.     

Free choice ethanol intake of laboratory rats under different social conditions

To study the effects of different kinds of social deprivation on voluntary ethanol (ETOH) intake male Wistar rats were housed by (a) individual caging, (b) contact caging (partial social deprivation), and (c) group caging (four individuals per cage). In the latter condition the individuals were separated once a week from each other for 24 h. The rats simultaneously received water 5%, 10% and 20% ETOH for a period of 14 weeks. Additional control animals received water. Isolated individuals drank significantly more alcohol than group-housed or contact-caged rats. After a few days they preferred the 20% solution. Circadian measures revealed a discontinuous intake of high doses (> 0.5 g/kg/h) during short time periods. Contact-caged rats consumed much less ETOH, but both the preference for 20% ETOH and the circadian course of intake were similar to those occurring after isolation. ETOH intake of group-housed individuals was low. These individuals preferred the 5% solution and continuously consumed small ETOH doses. During the period of short-term isolation they drank even more ETOH than long-term isolated individuals. In contrast to the latter, the enhancement of intake decreased after some weeks. It is suggested that the differences between the housing groups not only reflect different degrees of isolation stress, but may also be explained by a contribution of different reinforcing or aversive psychotropic effects of ETOH. Reduction of isolation stress is probably most important in the situation of short term separation, whereas dose-dependent reinforcement via social stimulation or sedation may affect the drug taking behavior under the other social conditions.     

黄芩苷标准品制备方法研究

采用醇提酸沉法提取黄芩苷粗品 ,再用分步精制的方法来制备黄芩苷标准品 ,所得标准品的熔点、含量与对照标准品一致。提示 :本法是制备黄芩苷标准品简便可行、收率高的方法     

Heparin-induced extracorporal low-density-lipoprotein precipitation (H. E. L. P.) to improve the recovery of hearing in patients with sudden idiopathic hearing loss

The pathogenesis of sudden hearing loss (SHL) is still not well understood. Possible causes include increased blood viscosity, microthrombosis or altered blood flow. Hypercholesterolemia, hyperfibrinogenemia and increased platelet aggregation are frequently observed in patients with SHL. The aim of this study was to investigate whether drastic lowering of plasma cholesterol and fibrinogen by selective extracorporal apheresis could have a beneficial effect on hearing recovery in these patients. Seven patients with SHL were treated with an extracorporal procedure removing fibrinogen and cholesterol from plasma. Six of the seven patients showed an immediate improvement in auditory thresholds following a single treatment of heparin-induced low-density lipoprotein precipitation. These findings indicate for the first time that acute and drastic removal of plasma fibrinogen and low-density lipoproteins may be an effective clinical method for the treatment of patients with SHL. Received: 19 February 1999 / Accepted: 6 May 1999     

LDL-C直接测定法在生化分析仪上的应用

用日本第一化学药品株式会社LDL—C试剂盒在BeckmanCX4型自动生化分析仪上直接测定血清LDL—C含量。方法批内CV 0 37%～ 1 11% ,批间CV为 2 11%～ 3 0 2 % (n =2 0 )。平均回收率为 98 9% ,在 8 10mmol/L浓度范围内呈良好线性关系。TG <5 0 0mmol/L时与聚乙烯硫酸沉淀法 (X1)及Friedewald(X2 )公式计算结果相关良好 ,回归方程分别为Y =0 988X1+0 0 47,r=0 95 1,Y =0 96 1X2 +0 0 5 2 ,r=0 930。LDL—C直接测定法简单、快速 ,用血量少 ,勿需沉淀分离 ,适宜于自动化分析。     

Ethanol self-administration in freely feeding and drinking rats: effects of Ro15-4513 alone,and in combination with Ro15-1788 (flumazenil)

Recent work in our laboratory demonstrated that Ro15-4513, a partial inverse benzodiazepine (BDZ) agonist, decreases ethanol (ETOH) self-administration in rodents under fluid deprivation conditions. The present study further examined the effects of Ro15-4513 (2.5 and 5.0 mg/kg) alone and in combination with Ro15-1788, (flumazenil) (8.0 and 16.0 mg/kg), a BDZ receptor antagonist on ETOH self-administration in freely feeding and drinking rats. Animals were trained to consume ETOH (11% v/v) using a limited access procedure. Measurements were taken at 10- and 60-min intervals. Ro15-4513 (2.5 and 5.0 mg/kg) markedly attenuated ETOH consumption at both intervals. The antagonistic actions of Ro15-4513 were completely blocked by the higher dose of flumazenil at both intervals; the lower dose failed to antagonize the Ro15-4513-induced reduction of ETOH intake. When flumazenil was given alone, both doses reduced ETOH self-administration at 60 min; although the magnitude of the antagonism was comparable to that of Ro15-4513 only with the highest does of flumazenil (16.0 mg/kg). Neither Ro15-4513 nor flumazenil alone or in combination significantly altered water intake at any of the tested doses. Rats pretreated with Ro15-4513 showed a substantial reduction in blood ethanol concentration (BEC) compared with the Tween-80 vehicle condition at the 10-min interval. However, the BEC of animals given Ro15-4513 in combination with flumazenil were similar to rats given Tween-80 vehicle. The present study extends our previous research by demonstrating that Ro15-4513 and flumazenil attenuate ETOH self-administration in non-food or water deprived rats. These studies suggest that the suppressant effects of Ro15-4513 and flumazenil on ETOH self-administration are associated with actions at the BDZ site of the GABA_A receptor complex. These data are discussed in relation to the possible mechanism(s) by which Ro-15-4513 and flumazenil exert their antagonism on ETOH self-administration.Portions of this work were presented at the Annual Meeting of the Research Society on Alcoholism under the symposium entitled GABA/BDZ Receptor Update, Marco Island, FL, June 10, 1991.We would like to dedicate this paper to the late Dr. Richard G. Lister, a friend, teacher, colleague and exceptional scientist who contributed substantially to the area of alcohol abuse and alcoholism. Over the past years, Dr. Lister investigated the interactions of alcohol with inverse benzodiazepine agonists and benzodiazepine receptor antagonists. His seminal and more recent papers played an important role in delineating the GABA benzodiazepine systems in the neurobehavioral actions of alcohol. Richard, we will miss you.