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1.
The effects of autoshaping procedures (paired vs. random) and sipper fluid (ethanol vs. water) on sipper-directed drinking were evaluated in male Long-Evans rats maintained with free access to food and water. For the paired/ethanol group (n=16), autoshaping procedures consisted of presenting the ethanol sipper (containing 0% to 28% unsweetened ethanol) conditioned stimulus (CS) followed by the response-independent presentation of food unconditioned stimulus (US). The random/ethanol group (n=8) received the sipper CS and food US randomly with respect to one another. The paired/water group (n=8) received only water in the sipper CS. The paired/ethanol group showed higher grams per kilogram ethanol intake than the random/ethanol group did at ethanol concentrations of 8% to 28%. The paired/ethanol group showed higher sipper CS-directed milliliter fluid consumption than the paired/water group did at ethanol concentrations of 1% to 6%, and 15%, 16%, 18%, and 20%. Following a 42-day retention interval, the paired/ethanol group showed superior retention of CS-directed drinking of 18% ethanol, relative to the random/ethanol group, and superior retention of CS-directed milliliter fluid drinking relative to the paired/water group. When tested for home cage ethanol preference using limited access two-bottle (28% ethanol vs. water) procedures, the paired/ethanol and random/ethanol groups did not differ on any drinking measures.  相似文献   

2.
The acute and chronic administration of delta 9-tetrahydrocannabinol (delta 9-THC) or cocaine were studied in rats trained to obtain all of their daily food by lever pressing during four equally-spaced 30-min periods with water and 5% or 7.5% ethanol solutions freely available. With 5% ethanol available, rats consumed almost all of their daily fluid intake as ethanol, while with 7.5% ethanol available, rats consumed water and ethanol solution in approximately equal amounts. Rats consumed more food pellets with 7.5% ethanol available than with 5% ethanol available. Acute administration of delta 9-THC produced a dose-dependent decrease of 5% ethanol intake and food pellets consumed with a small increase in water intake, especially after the higher doses. Acute administration of delta 9-THC also depressed food intake when 7.5% ethanol was available, but decreases in ethanol solution intake were small. Chronic administration of delta 9-THC initially decreased ethanol intake, but tolerance occurred to this effect, so that during chronic delta 9-THC administration ethanol intake not only recovered, but increased above control levels. When the chronic administration of delta 9-THC was discontinued, ethanol intake was increased for 1 (5% ethanol) to 3 (7.5% ethanol) weeks. Animals with initially high, or initially low, but not with initially moderate ethanol intake, accounted for the increased ethanol intake during chronic delta 9-THC administration and withdrawal. Acute cocaine administration, at doses up to 30 mg/kg, had little effect on eating and drinking; however, during chronic cocaine administration, ethanol intake gradually increased, an increase which was sustained during cocaine withdrawal. The increased ethanol drinking was confined to the first 6-h period after cocaine administration. These data suggest that the chronic administration and withdrawal of other drugs can increase ethanol intake in this rat model.  相似文献   

3.
目的:考察乙醇摄入对盐酸苯环壬酯控释片释放行为的影响。方法:测定盐酸苯环壬酯控释片中盐酸苯环壬酯原料在不同浓度乙醇磷酸盐缓冲液(pH3.0)中溶解度;关键辅料WSR-HM、WSR-LM在不同浓度乙醇磷酸盐缓冲液(pH3.0)中的黏度;以0%、5%、20%、30%、40%乙醇磷酸盐缓冲液(pH3.0)为释放介质,考察并比较盐酸苯环壬酯控释片的体外累积释放度,并采用扫描电镜观察释放介质中不同浓度的乙醇对盐酸苯环壬酯控释片薄膜衣的表面结构和释药孔的影响。据此分析乙醇影响盐酸苯环壬酯控释片体外释放的原因。结果:盐酸苯环壬酯在pH3.0磷酸盐缓冲液和5%、20%、30%、40%乙醇磷酸盐缓冲液(pH3.0)中的溶解度分别为39.6,47.3,84.7,171.4,235.4 mg·mL-1;WSR-HM、WSR-LM的黏度随释放介质中乙醇浓度的增加而下降;盐酸苯环壬酯控释片在pH 3.0磷酸盐缓冲液和5%乙醇磷酸盐缓冲液释放介质中的释放曲线相似(相似因子f2=74),但在20%、30%、40%乙醇磷酸盐缓冲液(pH3.0)释放介质中的释放度有显著变化;盐酸苯环壬酯控释片完全释放后,残留释药孔的直径分别为552,600,630,718,815 μm。结论:5%乙醇对盐酸苯环壬酯控释片的释放影响最小,而随着乙醇浓度的增加,乙醇通过改变盐酸苯环壬酯溶解度、WSR-HM及WSR-LM黏度和溶胀程度从而对盐酸苯环壬酯控释片的释放产生影响,并且乙醇浓度越大,体外释放越快。  相似文献   

4.
Water and ethanol consumption, blood and urine ethanol concentrations were measured in male rats aged 1.5 to 8 months. The animals had ethanol solutions (5-25%) and water as alternate fluid (two-bottle choice) or a 10% ethanol solution as a sole water source. In both cases, the rats did not exceed 7 g/kg of ethanol consumption per day. From 10 a.m. to 16 p.m. the blood ethanol concentration was no more than 0.1 g/l. Ethanol excretion with urine did not go beyond 0.1% of the daily dose. Ethanol consumption was increased by 1-2 g/kg a day if saccharin (0.125%) and sodium chloride (1%) were added to ethanol solution. In this case the withdrawal signs developed after ethanol consumption cessation.  相似文献   

5.
Chronic ethanol consumption potentiates acetaminophen (APAP) hepatotoxicity through enhanced NAPQI formation via CYP2E1 induction and selective depletion of mitochondrial glutathione. Because the prevalence of the interaction is extremely low given the use of APAP and the incidence of alcohol abuse, we studied the effects of ethanol dose and ethanol withdrawal on selective mitochondrial glutathione (GSH) depletion and APAP toxicity in liver slices. Rats were fed the Lieber-DeCarli diet containing ethanol (0, 7, 18, 27, and 36% total energy) for 6 weeks. The highest ethanol-containing diet (36% energy as ethanol) was replaced by control diet for 2, 5, 12, and 17 h. Maximal CYP2E1 induction was caused by 36% energy as ethanol diet (2.2-fold, p < 0.05 versus control). The activity and liver protein content returned to the control level 17 h after ethanol withdrawal. The 36% energy as ethanol diet caused maximal mitochondrial GSH depletion (51%, p < 0.05 versus control), which was restored 17 h after ethanol withdrawal (22.0 +/- 4.9 versus 11.7 +/- 1.7 nmol/mg protein of 0 h, p < 0.01). Elevated glutathione S-transferase-alpha release in liver slices (a measure of toxicity) was observed in rats fed 36% energy as ethanol diet (1 mM APAP: 69 +/- 10 versus 3 +/- 1% of control, p < 0.01). Enhanced toxicity disappeared when ethanol dose decreased and when ethanol was removed (7.2% ethanol: 3 +/- 1% and 17 h: 2 +/- 1%, p < 0.01 versus 0 h 36% energy as ethanol). In conclusion, high-dose ethanol potentiated APAP hepatotoxicity via CYP2E1 induction and selective mitochondrial GSH depletion. Mitochondrial GSH depletion quickly reversed when ethanol was withdrawn. The time window for both mechanisms to act in concert is narrow.  相似文献   

6.
Schedule-induced ethanol polydipsia: enhancement by saccharin   总被引:1,自引:0,他引:1  
The effect of adding sodium saccharin to a 5% ethanol solution on intake was examined. One set of animals were maintained at 80% of their free-feeding weight, in their home-cages with either 5% ethanol, or 5% ethanol-0.25% sodium saccharin as the only fluid available for three months (home-cage condition). A second set of animals were maintained in cages with automatic food dispensers that provided a 24 hr feeding regimen known to produce ethanol overdrinking (schedule-induced condition). These animals had 5% ethanol as their only available fluid for one month, followed by the 5% ethanol-0.25% sodium saccharin mixture for two months. No significant differences in ethanol intake were found between the 2 home-cage conditions (5% ethanol = 11.6 g ethanol/kg/day; 5% ethanol in 0.25% sodium saccharin = 11.7 g ethanol/kg/day. However, the addition of saccharin in the schedule-induced condition produced a marked increase in ethanol intake (5% ethanol = 13.1 g ethanol/kg/day; 5% ethanol in 0.25% sodium saccharin = 15.1 g ethanol/kg/day). The home-cage animals showed no sign of an abstinence syndrome upon substitution of water for ethanol. In the schedule-induced group, severe tonic-clonic seizures occured as a result of ethanol withdrawal.  相似文献   

7.
目的:对水蛭活性肽进行纯化,并对水蛭活性肽进行树脂纯化条件考察。方法:采用DA201-C大孔吸附树脂进行极性分离,后经D201阴离子交换树脂进行电荷分离,最终得到纯化的水蛭活性肽组分。结果:DA201-C大孔树脂,上样肽浓度20 mg·mL-1,流速1.0 BV·h-1,依次用25%乙醇、50%乙醇和75%乙醇溶液洗脱,各洗脱部位得率及活力较高,但总体活性成分被分散,以上各洗脱部位经D201离子交换树脂,pH 4.0,上样肽浓度30 mg·mL-1,流速3.0 BV·h-1,分别用2.5%氯化钠的25%乙醇、2.5%氯化钠的50%乙醇、2.5%氯化钠的75%乙醇溶液洗脱,2.5%氯化钠的25%乙醇和2.5%氯化钠的50%乙醇洗脱部位有明显的抗凝活性,经过分析性RP-HPLC验证后,基线平稳,各组分分离度良好。结论:经DA201-C大孔树脂和D201离子交换树脂纯化后的水蛭活性肽,2.5%氯化钠的25%乙醇和2.5%氯化钠的50%乙醇洗脱部位活力较高,分离度好。  相似文献   

8.
目的:筛选冬凌草的抗炎有效部位并对有效部位进行初步表征.方法:冬凌草采用梯度极性溶剂水、25%乙醇、50%乙醇、75%乙醇及100%乙醇分别提取,提取物通过蛋清致大鼠足跖肿胀试验以确定抗炎有效部位;并对有效部位采用MS分析,HPLC测定主成分冬凌草甲素的含量.结果:冬凌草100%乙醇提取物对大鼠足跖肿胀有明显的抑制作用,MS分析提取物中明显含有冬凌草甲素及其他贝壳杉烷类二萜,HPLC测定无水乙醇提取冬凌草甲素的提取率为0.174 6%.结论:冬凌草100%乙醇提取物组分具有明显的抗炎作用,为冬凌草的抗炎有效部位,为其临床抗炎提供依据.  相似文献   

9.
Rats were induced to consume concentrations of ethanol between 5% and 10% (w/v) using the schedule-induced polydipsia technique. Although the substitution of ethanol solutions for water disrupted the usual post-pellet pattern of drinking, large amounts of ethanol were consumed and sound-induced convulsions were observed during ethanol withdrawal. In subsequent experiments, other rats chose 5% and sometimes 10% ethanol solutions over water where both water and ethanol were freely available during the first session of exposure to ethanol. Convulsions and wild running behavior could be observed in some of these rats after only 8 days of drinking, even though ethanol was freely available at all times. Use of the schedule-induced polydipsia technique served to bring the rats into early contact with the ethanol, but rats that received the same number of food pellets in a dish rather than by the schedule drank almost as much ethanol as did the rats receiving ethanol by the schedule. Rats with free access to food pellets drank very little ethanol.  相似文献   

10.
Three experiments investigated the relationship between ethanol consumption and the percentage ethanol-derived kilocalories contained in liquid diets. Rats were chronically maintained on diets where different concentrations of ethanol (10%, 12%, 14%) were added to Metrecal so that 41%, 49% and 57% of all kilocalories consumed were derived from ethanol. The ethanol-Metrecal diet served as the sole source of calories. Results demonstrated that rats can be maintained fromextended time periods on diets where ethanol contributed approximately 50% of the daily kilocalories. Inspection of consummatory profiles revealed that an initial decrease occurred in volume of diet consumed when levels of ethanol were increased. This was followed by a gradual increase in the level of consumption until a new asymptotic level was established. Grams of ethanol/kg of body weight remained relatively constant over the range of ethanol concentrations employed. The results were discussed in respect to three factors controlling consummatory behavior-sensory stimuli, caloric intake and quantity of ethanol ingested.  相似文献   

11.
Rats were maintained in cages with automatic food dispensers that provided a 24 hr feeding regimen known to produce schedule-induced ethanol polydipsia. For ten days water was the only available fluid; then for 17 days either 5% or 10% ethanol replaced water. The ethanol concentrations were then switched between groups for a final 13 days. Ethanol intake increased for both groups over the first seven days and then reached asymptote. The daily intake (ml) of 5% ethanol was two times that of 10%, resulting in no difference between groups in g/kg ethanol consumed. When the concentrations were switched, g/kg/day dropped, but returned to previous levels within seven days. Again intake (ml) of 5% was two times that of 10% but groups did not differ in g/kg/day. Mean blood ethanol concentration at 9:30 hr was 75.0 mg/100 ml with 5% ethanol and 127.8 mg/100 ml with 10% ethanol.  相似文献   

12.
The effect of ethanol on the cyclic AMP system of the dog fundic mucosa was studied in vitro. The gastric mucosal content of cyclic AMP was increased by 2.5% ethanol, whereas 10 and 20% ethanol decreased the mucosal content of cyclic AMP. The activity of adenylate cyclase was increased by 2.5 and 5% ethanol, whereas 10% ethanol did not significantly affect it. The activity of cyclic AMP phosphodiesterase was inhibited by ethanol in a competitive manner. The increase in the gastric mucosal content of cyclic AMP, induced by low concentrations of ethanol, is apparently due to the stimulation of adenylate cyclase and inhibition of phosphodiesterase. Changes in the phosphodiesterase or adenylate cyclase activites do not explain the decrease of the mucosal content of cyclic AMP by higher concentrations of ethanol. The mechanism of the decrease is discussed.  相似文献   

13.
The enhancement of voluntary self-administration of ethanol by sucrose or saccharin was tested in conjunction with measurements of blood ethanol levels. Adult male rats were given access to both tap water and one of five solutions: 0.125% saccharin, 10% sucrose, ethanol, saccharin+ethanol, or sucrose+ethanol. The rats receiving the sucrose+ethanol solution drank consistently more ethanol (>5 g/kg/day) than did the rats receiving the saccharin+ethanol solution (<3 g/kg/day) or ethanol only (<2 g/kg/day). Both sweetened solutions produced higher ethanol consumption during these periods than ethanol alone. However, no significant differences in blood ethanol levels were found between the sucrose+ethanol and saccharin+ethanol conditions, when tested at different intervals on Day 44 or Day 45 of ethanol consumption. Following 45 days of consumption, no change in the bicuculline seizure threshold was observed in the ethanol-consuming rats compared to the controls. In a separate study using 90 naive rats, rats were gavaged with ethanol (1, 2, or 3 g/kg) containing either 10% sucrose (n=10 for each dose of ethanol), 0.125% saccharin (n=10 for each dose of ethanol), or ethanol alone (n=10 for each dose of ethanol), and blood was collected from the tip of the tail 30, 60, 180, 300, and 540 min later and analyzed for ethanol concentrations. Sucrose significantly decreased the resultant blood ethanol levels at several time points following gavage. These results indicate that sucrose can significantly alter blood ethanol levels and that chronic self-administration of a sweetened ethanol solution for 6 weeks does not produce ethanol dependence.  相似文献   

14.
The conditions under which a drug is administered often alter the behavioral effects of that drug. The present study examined the effect of changes in response dependence on the discriminative stimulus effects of ethanol. Six Long-Evans rats were trained to discriminate 1000 mg/kg, interperitoneal (i.p.) ethanol from saline. A dose-effect curve was then obtained using i.p. doses of 100, 320, 560, 1000, 1320 and 1560 mg/kg ethanol. Ethanol doses of 1000 mg/kg and greater produced more than 80% ethanol-lever selection. The rats were then trained to orally self-administer 10% weight/volume ethanol and tested to determine if self-administered oral ethanol would substitute for experimenter administered i.p. ethanol. A mean self-administered ethanol intake of 1114 mg/kg (+/-156 mg/kg) produced 83% ethanol-lever responding. Restricted access to 560 mg/kg of self-administered ethanol resulted in 33% i.p. ethanol-lever responding. Doses of 100 and 320 mg/kg ethanol did not substitute for i.p. ethanol. These data show that orally self-administered ethanol can produce discriminative stimulus effects that are similar to i.p. experimenter-administered ethanol and that orally self-administered ethanol produces centrally-mediated discriminative stimulus effects.  相似文献   

15.
The present study reports on the development of a multiple schedule procedure of oral ethanol self-administration in cynomolgus macaques. Six adult cynomolgus macaques (four female, two male) were trained to self-administer ethanol and water under a 60 min, four-component multiple schedule of ethanol and water access with 1 g food pellets presented every 900 s (fixed-time 900 s). Water was available for the first and third 15 min components, ethanol in the second and fourth components. Total ethanol dose was stable at between 1-1.25 g/kg at ethanol concentration of 4%, 6% and 8%. Subsequently water was replaced with a sweetened drink (sugar-free Tang powder, General Foods). Ethanol and Tang were self-administered in similar volumes and both served as reinforcers compared with water. Acute pretreatment with 0.25 to 1.5 g/kg of intragastrically gavaged (i.g.) ethanol failed to alter ethanol or Tang self-administration significantly despite producing mean blood ethanol levels of up to 199 mg/dl when combined with self-administered ethanol. However, 1.0 g/kg i.g. ethanol administered for 15 consecutive days significantly decreased ethanol self-administration by 23%. The results suggest that ethanol self-administration under a multiple schedule is insensitive to alteration by acute ethanol pretreatment, but can be decreased by more prolonged chronic ethanol pretreatment.  相似文献   

16.
Purpose. Manufacturing processes expose protein pharmaceuticals to organic solvents that may perturb the native folded state, increasing the potential for irreversible aggregation or surface adsorption. The aim of this study was to characterize the conformational states of human growth hormone (hGH) in aqueous ethanolic solutions.Methods. The higher order structure of hGH was investigated using far- and near-UV circular dichroism (CD) and fluorescence spectroscopy as orthogonal techniques, and the hydrodynamic size was monitored using dynamic light scattering.Results. CD data suggested that the secondary structure of hGH remained unchanged up to 50\% (v/v) ethanol, but the tertiary structure was perturbed at ã20% ethanol. Fluorescence anisotropy, however, showed that the mobility of the buried Trp residue was restricted even at 30% ethanol, suggesting a differently packed structural core in 30% ethanol relative to the native structure. Consistent with this result, thermal unfolding of hGH in 30% ethanol was more facile compared to that in 0% and 20% ethanol. At >40% ethanol, fluorescence data were consistent with increased solvent exposure of the tryptophan.Conclusions. The results point to progressive unfolding of hGH that increases solvent exposure of the hydrophobic core as a function of ethanol concentration and suggest that non-native intermediate states are populated in 30–60% ethanol.  相似文献   

17.
紫菀、款冬配伍中紫菀的祛痰研究   总被引:1,自引:0,他引:1  
目的:借助祛痰实验,筛选紫菀的有效部位及款冬的相须部位。方法:以酚红排泄量为指标,确定紫菀、款冬的提取方法分别为30%乙醇回流提取、水提取。将提取物醇沉,分别得到3个部位:60%乙醇部位;90%乙醇部位;90%乙醇溶液部位。结果:紫菀的有效部位是紫菀90%乙醇部位(RA2),款冬的相须部位是90%乙醇溶液部位(FF3)。结论:紫菀的有效部位是极性较大的部位,款冬的相须部位则是极性较小的部位。  相似文献   

18.
葡萄籽原花青素降血脂药效部位筛选   总被引:2,自引:2,他引:0  
目的:研究不同组分葡萄籽原花青素降血脂药效。方法:采用不同浓度乙醇渗漉提取、大孔树脂分离纯化,制得10%、30%、50%、70%乙醇部位葡萄籽原花青素提取物,建立大鼠高血脂模型,分别测定各组血清甘油三酯(TG)、总胆固醇(TC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)的含量,以及Lee’S指数和脏器指数,对各提取物进行药效学研究,确定葡萄籽原花青素降血脂有效部位。结果:葡萄籽原花青素提取物10%、30%、50%乙醇部位具有明显降低高血脂大鼠模型的TG的含量(P<0.01);同时50%乙醇部位还可以明显降低高血脂大鼠模型的ALT和AST含量(P<0.01);10%、30%、50%、70%乙醇部位能抑制Lee’S指数的升高(P<0.01或P<0.05);10%乙醇组显著升高肾脏指数;10%、30%、50%、70%乙醇组能显著升高脾脏指数(P<0.01);10%、50%、70%乙醇组能显著降低总脂指数(P<0.01)。结论:50%乙醇部位葡萄籽原花青素提取物为葡萄籽降血脂有效部位。  相似文献   

19.
目的系统考察先天性嗜酒(FH/Wjd)大鼠嗜酒的行为特性。方法采用双瓶(5%或10%乙醇和自来水)自由选择的方法,观察FH/Wjd大鼠的饮酒量、饮水量和乙醇偏爱率,并进一步探讨FH/Wjd大鼠饮酒的昼夜差异性;在乙醇剥夺实验中,研究乙醇剥夺24h对FH/Wjd大鼠饮酒量和乙醇偏爱率的影响;选用固定比率(FR1)实验程序,探讨FH/Wjd大鼠操作性自身饮酒的行为特点。结果在双瓶自由选择饮酒实验中,给予5%乙醇,大鼠的饮酒量为(4.3±0.2)g·kg-1·d-1,饮水量为(20.1±2.3)g·kg-1·d-1,乙醇偏爱率为(82.9±2.0)%;给予10%乙醇,大鼠的饮酒量为(6.4±0.2)g·kg-1·d-1,饮水量为(37.2±2.7)g·kg-1·d-1,乙醇偏爱率为(69.2±2.0)%,与5%乙醇相比较,饮酒量和饮水量显著增大,但乙醇偏爱率明显降低。FH/Wjd大鼠的饮酒行为呈明显的昼夜节律,夜间饮酒量和乙醇偏爱率均显著高于白天,夜间饮水量虽呈增加趋势,但差异无显著性。FH/Wjd大鼠乙醇剥夺24h,再次给酒后1h的饮酒量增加37.7%,乙醇偏爱率增加22.1%;再次给酒后24h的饮酒量增加15.6%,乙醇偏爱率存在增高趋势,但差异无显著性。FH/Wjd大鼠操作性自身饮酒行为训练13d后,连续测试3d,操作性饮酒行为的偏爱率为49%~64%。结论FH/Wjd大鼠具有饮酒量大和乙醇偏爱率高的特点,存在明显的乙醇剥夺效应,并可在短期内建立操作性自身饮酒行为,是一种理想的先天嗜酒动物模型。  相似文献   

20.
Dippers filled with water or an ethanol solution were presented to male Wistar rats contingent on lever-pressing under a concurrent fixed-ratio 1 (water) fixed-ratio 1 (ethanol) schedule. During Phase I, when maintenance feedings were given during instead of following the daily 3-h sessions, the feedings increased drinking of both 8% (w/v) ethanol and water, with 8% ethanol being consumed in greater volumes than water. In Phase II, a 28-day transitional period from the food-deprived to the food-satiated state, continuous access to food during 3-h sessions moderately decreased 8% ethanol intake, and increased water intake and total liquid intake (water plus 8% ethanol). In Phase III, concurrent water and ethanol intake of food-satiated rats was compared over two identical series of ethanol concentrations (8, 11.3, 16, 22.6, 32, and 8% retest). Food was freely available in both the operant conditioning chambers and home cages. The number of dipper presentations of ethanol exceeded presentations of water for each rat at each concentration studied. Presentations of water were low in number and did not vary with the ethanol concentration. As the ethanol concentration was increased, the number of ethanol presentations decreased, while the quantity consumed (mg/100 g body weight/h) generally increased.  相似文献   

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