AMPK基因在C57BL／6J小鼠糖脂代谢中的作用

目的研究腺苷酸活化蛋白激酶（AMPK）基因在C57BL／6J小鼠糖脂代谢中的作用。方法分别取5周龄AMPK基因敲除（AMPK-KO）小鼠和C57BL／6J对照小鼠各24只,分为正常饲料（ND）喂养和高脂高糖饲料（HFD）喂养两组。喂养12周,每两周测定小鼠禁食4h血糖（FBG）,实验结束前行口服糖耐量实验（OGTT）,解剖取样,检测血生化指标、脂酶活性及相关蛋白的表达。结果AMPK-KO小鼠血糖、TC、LDL-C、HbA1c、6-磷酸葡萄糖脱氢酶（G6PD）活性、糖原合成酶激酶（GSK）活性、肝脏PPAR7蛋白表达量明显高于对照小鼠（P〈0．05）;其胰岛素含量、肝糖原含量、肌糖原含量、肝脂酶（HL）活性、脂蛋白酯酶（LPL）活性、总脂酶活性、葡萄糖激酶（GK）活性、肝组织P-AMPK蛋白、葡萄糖转运蛋白4（GluT-4）蛋白的表达量低于对照组（P〈0．05）。结论AMPK基因通过调节C57BL／6J小鼠糖脂代谢,在T2DM的发病中起重要作用。     

Melatonin reduces cholesterol accumulation and prooxidant state induced by high cholesterol diet in the plasma, the liver and probably in the aorta of C57BL/6J mice

We examined the hypolipidemic and antioxidative effects of melatonin in plasma, liver and aorta of C57BL/6J mice fed on a high cholesterol (HC) diet. Mice were fed normal mice chow containing 1.5% cholesterol and 0.5% cholic acid for 4 months with or without melatonin (10 mg/L in drinking water) treatment. HC diet was observed to increase cholesterol, triglyceride and diene conjugate (DC) levels in plasma and liver. There was a tendency towards an increase in cholesterol level in the aorta following HC diet. In addition, aortic DC levels were higher than those of control group. No fatty streaks or plaques developed in the aorta of mice following HC diet, but in some sections, derangement of the endothelial layer was detected. Melatonin treatment was found to reduce plasma, liver cholesterol and DC levels as well as liver triglyceride levels in hypercholesterolemic mice. Aortic cholesterol and DC levels were also reduced in hypercholesterolemic mice when given melatonin, although not statistically significant. There were no differences in aortic histopathological findings of mice fed on a HC diet with and without melatonin treatment. In conclusion, our results indicate that melatonin reduces HC diet-induced cholesterol accumulation and prooxidant state in the plasma, liver and probably in the aorta.     

Characterization of survival and phenotype throughout the life span in UCP2/UCP3 genetically altered mice

In the present investigation we describe the life span characteristics and phenotypic traits of ad libitum-fed mice that overexpress UCP2/3 (Positive-TG), their non-overexpressing littermates (Negative-TG), mice that do not expression UCP2 (UCP2KO) or UCP3 (UCP3KO), and wild-type C57BL/6J mice (WT-Control). We also included a group of C57BL/6J mice calorie-restricted to 70% of ad libitum-fed mice in order to test partially the hypothesis that UCPs contribute to the life extension properties of CR. Mean survival was slightly, but significantly, greater in Positive-TG, than that observed in Negative-TG or WT-Control; mean life span did not significantly differ from that of the UCP3KO mice. Maximal life span did not differ among the ad libitum-fed groups. Genotype did not significantly affect body weight, food intake, or the type of pathology at time of death. Calorie restriction increased significantly mean and maximal life span, and the expression of UCP2 and UCP3. The lack of difference in maximal life spans among the Positive-TG, Negative-TG, and UCP3KO suggests that UCP3 does not significantly affect longevity in mice.     

三种品系小鼠对伴刀豆球蛋白A所致急性肝损伤的耐受性比较研究

目的：应用不同剂量伴刀豆球蛋白 A（ConA）诱导三种不同品系小鼠急性肝损伤,比较肝酶变化、死亡率和肝组织病理学变化。方法分别用6、12、20和30 mg·kg-1 ConA 处理 C57BL/6J、BABL/c 和 KM 小鼠,8 h 后对比观察急性肝损伤动物血清酶学及肝组织病理学变化情况。结果在6 mg·kg-1 ConA 的作用下,三个品系小鼠均被成功制造出急性肝损伤模型;在12 mg·kg-1 ConA 作用下,KM 小鼠血清 ALT 和AST 分别为（1006.8±12.1） U/L 和（1391.8±13.4）U/L,显著高于 BABL/c 小鼠[（75.7±0.5）U/L 和（284.7±23.4） U/L）和 C57BL/6J 小鼠（104.4±32.2）U/L 和（492.2±12.3）U/L,P 均〈0.05];同样,KM 小鼠肝指数和脾指数分别为（5.4±0.3）和（0.7±0.5）,均显著高于 BABL/c 小鼠[（5.2±0.4）和（0.6±0.3）和 C57BL/6J 小鼠（5.0±0.6）和（0.6±0.2）,P 均〈0.05];在20 mg·kg-1 ConA 作用下,三组小鼠血清 AST 和 ALT 水平无统计学差异,但 BABL/c 小鼠（4/10）和 C57BL/6J 小鼠（5/10）死亡率显著高于 KM 小鼠（1/10）;在30 mg·kg-1 ConA 作用下,三个品系小鼠死亡率均较高（KM 小鼠为30%,BABL/c 和C57BL/6J 小鼠均为100%）。结论不同品系的小鼠对 ConA 的耐受性不同,KM 小鼠对 ConA 的耐受性明显优于BABL/c 小鼠和 C57BL/6J 小鼠,且呈剂量依赖性。     

链脲菌素剂量对C57BL/6J小鼠糖尿病诱导效应的影响

目的 观察不同剂量链脲菌素(STZ)对C57BL/6J小鼠糖尿病诱导效应的影响,探讨其量效关系及最佳剂量范围.方法 将C57BL/6J小鼠按数字随机法分为9个STZ剂量组(A～I组,STZ分别为30、60、80、100、120、150、180、210、240 ms/kg体重),每组15只,腹腔注射;1个对照组,10只,腹腔注射等体积缓冲液.观察各组血糖、体重、血胰岛素和45 d生存率的变化,分析其与STZ剂量的关系.同时取A、C、G及对照组小鼠胰腺、肾脏组织做病理学检杏,并行免疫组化观察胰腺胰岛素及肾脏CD<,68>的表达.结果 C～G组较对照组血糖增高、体重及血胰岛素含量较对照组下降非常显著(P<0.05),且STZ剂量与血糖呈正相关(r=0.984,P<0.05),与血胰岛素含量呈负相关(r=-0.994,P<0.05).C～G组成模率达86.7%～100%,显著高于A、B组的0和40%(P<0.05);45 d生存率为46.7%～73.3%,显著高于H、I组的13.3%和0(P<0.05).A组胰腺、肾脏组织未见明显破坏;C组及G组出现典型的胰岛萎缩变形,胰岛素分泌颗粒减少,肾小球系膜外基质沉着及球周臣噬细胞浸润.结论 C57BL/6J小鼠腹腔注射STZ以80～180 mg/kg体重的剂量制模率高、生存率高,且靶器官损伤典型;该剂量与血糖呈正相关,与血胰岛素含量呈负相关.     

Experimental scoliosis in melatonin-deficient C57BL/6J mice without pinealectomy

The etiology of idiopathic scoliosis is unknown. Scoliosis with many characteristics closely resembling those seen in idiopathic scoliosis has been produced in young chickens and bipedal rats after pinealectomy. In this study, we induced experimental scoliosis in C57BL/6J mice without pinealectomy and melatonin treatment suppressed the development of scoliosis. A total of 100 mice were divided into four groups: 20 quadrupedal mice served as controls; 30 mice underwent resection of two forelegs and tail at 3 wk of age (bipedal mice); the remaining 20 quadrupedal and 30 bipedal mice received intraperitoneal melatonin (8 mg/kg BW) at 19:00 hr daily. Before killing, blood samples were collected in the middle of dark cycle and melatonin levels were measured by radioimmunoassay. Spine X-ray and helical 3D-CT were examined after killing at 5 months of age. The bipedal mice without a tail were able to walk with standing posture, whereas the quadrupedal mice did not walk with standing posture. In C57BL/6J mice, the serum melatonin was reduced to nearly zero; however, the normal level was restored in both bipedal and quadrupedal mice after the injection of melatonin. Scoliosis with rib humps developed in 29 of 30 bipedal and in five quadrupedal mice. None of mice with melatonin treatment developed scoliosis. The results suggest that melatonin deficiency in bipedal mice appears to play crucial role for development of scoliosis. Also the restoration of melatonin levels prevents the development of scoliosis.     

Anticonvulsant activity of melatonin against seizures induced by quinolinate, kainate, glutamate, NMDA, and pentylenetetrazole in mice

Abstract: Melatonin was tested in an ongoing attempt to find the endogenous antagonists of quinolinic acid, an endogenous convulsant. Among a great number of metabolites that have been tried before, only a few were found (cerulein and quinaldic acid in mice and kynurenic acid in rats). In SHR (bred from Swiss) male mice, intracerebroventricular (i.c.v.) pretreatment with melatonin (1.25–10.0 μg) attenuated (in the descending order of potency) the convulsant effect of i.c.v. administered kainate, quinolinate, glutamate, N-methyl-D-aspartate, and pentylenetetrazole. Melatonin was ineffective against i.p. administered pentylenetetrazole. Systemically (intraperitoneal, i.p.) administered melatonin (12.5–100.0 mg/kg) attenuated the convulsant effect of quinolinate, while the action of other convulsants used remained unaltered. It is suggested that melatonin could be tried against grand ma1 seizures in epileptic patients.     

BAPN-induced rodent model of aortic dissecting aneurysm and related complications

BackgroundThe aim of this study was to investigate the effects of beta-aminopropionitrile (BAPN) on the arterial walls of rodents, and to analyze the gross or pathological changes of arterial and other tissues of rodents treated with BAPN at different concentrations or doses.MethodsEighteen SPF SD rats (4–5-week old) were divided into three groups: SD-0.2 (Group A), SD-0.4 (Group B), and SD-0.6 (Group C). The groups A, B and C were given 0.2%, 0.4%, and 0.6% BAPN solution, respectively, as drinking water for seven weeks. Forty SPF C57BL/6 mice (3-week old) were randomly divided into four groups: C57-0.2 (Group D), C57-0.4 (Group E), C57-0.6 (Group F) and the control group and given 0.2%, 0.4%, or 0.6% BAPN or distilled water as drinking water, respectively, for seven weeks. All experimental animals were free to drink water. The aortas were dissected and visually examined. At the same time, hematoxylin and eosin (HE) staining was performed in aorta tissue. The vascular diameter and area of the middle membrane were measured with IPP (Image-Pro Plus 6.0).ResultsBAPN treatment significantly affected the water intake and weight gain of rats and mice. BAPN also caused thickening of the membrane in the aortas of rats and mice, and irregularity in the arrangement of elastic fibers. These pathological changes are similar to the pathological changes observed in human aneurysms. The incidence of dissecting aneurysm in C57 mice was higher than that of Sprague Dawley (SD) rats.ConclusionsBAPN at a concentration of 0.4% was feasible to produce an animal model of dissecting aneurysm. In SD rats, the rate of pathological changes and other complications, such as intestinal rupture and scoliosis, was higher than the rates of dissecting aneurysm.     

Association between ethanol and sucrose intake in the laboratory mouse: exploration via congenic strains and conditioned taste aversion

BACKGROUND: A substantial body of literature indicates that intakes of "sweet" solutions and ethanol are positively correlated across inbred strains of rats and mice but there has been speculation that the correlation is fortuitous and there is no agreement on the underlying mechanism. METHODS AND RESULTS: We assessed the correlation between intake of sucrose and ethanol in congenic mice created by backcrossing alleles favoring sucrose intake from the BXD RI-5 strain into DBA/2J. In addition, to probe more specifically the interrelationship between intake of the two solutions, we examined aversion generalization from sucrose to ethanol in C57BL/6J mice. Among the congenic mice, a statistically significant product-moment correlation of r = 0.36 (p < 0.02) was found between 6-hr intake of sucrose corrected for differences in baseline water intake and preference for 10% ethanol presented in a 96-hr 2-bottle test. Furthermore, C57BL/6J male mice conditioned to avoid a 0.2 M sucrose solution generalized their aversion to a 10% ethanol solution presented in the same 2-bottle test, drinking 42.1 +/- 9.38% (mean +/- SE) of their total fluid intake from the ethanol tube, compared with the control group mean of 69.86 +/- 8.84%. CONCLUSIONS: The positive association between intake of sucrose and ethanol in congenic mice provides strong evidence that the previously demonstrated genetic correlation between intake of these solutions is not the result of fortuitous fixation of unrelated alleles and provides suggestive evidence that, at least in the B6/D2 lineage, the genetic association between intakes of the two solutions reflects close linkage or the pleiotropic effects of the same genes. The demonstration that a conditioned taste aversion to sucrose generalized to ethanol in the C57BL/6J inbred mouse strain is an extension of similar observations in outbred rats and specifically demonstrates that intake of the two solutions is controlled by some of the same physiologic or neurological processes and thus is consistent with the pleiotropic interpretation of the genetic correlation.     

旋毛虫抗C57BL/6小鼠体内Hepa1-6肝癌细胞作用的研究

目的观察旋毛虫对C57BL/6小鼠体内Hepa1-6肝癌细胞生长的抑制作用。方法将C57BL/6小鼠随机分成8组,每组10只。第1和5、2和6、3和7组分别感染未处理旋毛虫、^60Co处理和紫外线处理旋毛虫,4和8组为不感染旋毛虫对照组,1～4组和5～8组分别于接种旋毛虫前7 d和接种后11 d接种Hepa1-6肝癌细胞。荷瘤后25 d后处死小鼠,测量肿瘤体积、重量及脾脏CD3^＋、CD4^＋、CD8^＋淋巴细胞数量。结果未处理旋毛虫组、^60Co处理组和紫外线处理组小鼠肿瘤体积和重量均显著低于对照组（P〈0.05）;脾脏CD3^＋、CD4^＋百分率和CD4^＋/CD8^＋、CD4^＋/CD3^＋的比值显著高于对照组（P〈0.01或P〈0.05）。结论未处理的旋毛虫、经^60Co和紫外线处理的旋毛虫对C57BL/6小鼠体的Hepa1-6肝癌细胞的生长均有抑制作用,未处理旋毛虫的抑瘤效果最好。     

Discriminative stimulus effects of ethanol in C57BL/6J and DBA/2J inbred mice

BACKGROUND: Two of the most widely used mouse strains for studying the behavioral effects of ethanol are C57BL/6J (B6) and DBA/2J (D2) mice. These strains exhibit marked differences in behavioral and physiological responses to ethanol. The subjective discriminative stimulus effects of ethanol may play a role in ethanol abuse, but the discriminative stimulus profile of ethanol has not been compared in B6 and D2 mice. Examination of the discriminative stimulus effects of ethanol in B6 and D2 mouse strains may enhance our understanding of the relationship between the subjective effects of ethanol and other ethanol-induced behavioral effects. METHODS: Twelve adult male C57BL/6J mice and 12 male DBA/2J mice were trained to discriminate 1.5 g/kg ethanol from saline in daily 15 min, milk-reinforced operant sessions. After training, ethanol substitution and response-rate suppression dose response curves were determined for ethanol, midazolam, diazepam, pentobarbital, pregnanolone, 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), dizocilpine, and morphine. RESULTS: D2 mice learned the ethanol discrimination significantly more quickly than did B6 mice. Ethanol, midazolam, pregnanolone, and dizocilpine fully substituted for ethanol in both strains. Pentobarbital was more potent in producing ethanol-like discriminative stimulus effects in D2 than B6 mice. Midazolam and diazepam were significantly more potent in suppressing response rates in D2 than B6 mice. Morphine failed to substitute for ethanol in either strain, but the ED50 for morphine suppression of responding was significantly lower in B6 than D2 mice. CONCLUSIONS: The initial stimulus effects of 1.5 g/kg ethanol may be more salient in D2 than B6 mice. This does not appear to result from differences in the neurotransmitter systems that mediate ethanol's discriminative stimulus effects. In both strains, gamma-aminobutyric acid-positive modulators and a noncompetitive NMDA antagonist substituted for ethanol. However, strain differences did exist in the potency of gamma-aminobutyric acid-positive modulators and morphine for suppressing operant responding.     

Factors affecting the infection of the D variant of encephalomyocarditis virus in the B cells of C57BL/6J mice

Summary The D variant of encephalomyocarditis viras is capable of infecting most inbred strains of mice. However, only certain strains are susceptible to the diabetogenic effect of this viras. In order to understand why some inbred strains do not become diabetic, the pathogenesis of infection was studied in diabetes-resistant C57BL/6J mice. It was the purpose of the investigation to ascertain whether specific host defense factors might play a crucial role in the mechanism of resistance. To determine whether perturbations of the immune response would alter the resistance of these animals, mice were treated with a high dose (1.15 mmol/kg body weight) of the T- and B-cell toxin cyclophosphamide prior to infection with the D variant. This treatment did not induce overt diabetes or glucose intolerance in the mice tested 7 days after infection. Based on this finding, it appeared likely that resistance to the D variant is conveyed by some factor other than cell-mediated immunity. A likely candidate to control this viral infection is the interferon system. To investigate this possibility, C57BL/6J mice were infected with the D variant and the concentrations of serum interferon titred at various intervals thereafter. In contrast to previous reports with diabetes susceptible mice, C57BL/6J mice were found to generate a substantial interferon response against this variant, with peak levels found in the serum at 24 h following infection. Additional studies were performed in which mice were treated with antibody to mouse interferon alpha/beta at the time of infection and again 3 days after infection with the D variant. Sixty percent of the animals treated in this manner became glucose intolerant. The results of these studies indicate that the interferon system is a critical determinant of resistance to the diabetogenic effect of the D variant in C57BL/6J mice.     

Secretion and effect of somatostatin in early stages of the diabetic syndrome in C57BL/KsJ-mdb mice

Summary In a previous study in C57BL/KsJ (mdb) mice aged 12 to 90 days, we observed alterations in the secretion of insulin and somatostatin and in the inhibitory effect of the latter upon insulin secretion. This study explores whether hormonal alterations are to be found in the very early stages of the diabetic syndrome, i. e. between ages 4 and 12 days. The results demonstrate two distinct phases in the development of the syndrome: (a) up to age 6 days, the perifused slices of pancreata of control animals present biphasic glucose-induced patterns of insulin and somatostatin secretion, whereas the diabetic animals show a diminished first peak of insulin secretion, but a similar pattern of somatostatin secretion, to that of the control animals; (b) between ages 7 and 12 days, the pancreata of diabetic mice exhibit insulin hypersecretion in basal conditions, and an absence of the first secretion peak and insulin hypersecretion in the second phase in response to glucose stimulation. The glucose-induced pattern of somatostatin secretion presents hormonal hypersecretion in both phases. B-cell sensitivity to the inhibitory effect of somatostatin is diminished in mdb mice of the above-mentioned groups, an alteration which becomes more evident as diabetes evolves. The results show that, in very early stages of the evolution of the diabetic syndrome in C57BL/KsJ (mdb) mice, there are already alterations in insulin and somatostatin secretion patterns and in the inhibitory effect of the latter on insulin secretion.     

Increased consumption but not operant self-administration of ethanol in mice lacking the RIIbeta subunit of protein kinase A

BACKGROUND: Accumulating evidence indicates that adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is involved in the neurobiological responses to ethanol. Previous reports indicate that mice lacking the RIIbeta subunit of PKA (RIIbeta(-/-)) voluntarily consume more ethanol than wild-type controls (RIIbeta(+/+)) using 2-bottle testing procedures. Although such procedures primarily measure consummatory behavior, operant self-administration procedures allow analysis of consummatory as well as appetitive or "ethanol-seeking" behavior (i.e., lever pressing is required to gain access to the ethanol solution). Therefore, we determined whether the high ethanol consumption characteristic of RIIbeta(-/-) mice would be complemented by increased appetitive ethanol-seeking behavior in an operant paradigm. METHODS: RIIbeta(-/-) (n=8) and RIIbeta(+/+) (n=8) mice were initially sucrose-faded until they were lever responding for nonsweetened ethanol (10, 14, and 18%). Following the self-administration testing, RIIbeta(+/+) and RIIbeta(-/-) mice were given access to 2 bottles, one containing water and the other ethanol to replicate the voluntary ethanol drinking data previously from our laboratory. Finally, immediately after voluntary consumption all mice were again tested for self-administration of 10% ethanol. Alterations in the reinforcement schedule were also explored as RIIbeta(+/+) and RIIbeta(-/-) mice were tested for self-administration of 10% ethanol at FR-3 and FR-5 schedules. RESULTS: The RIIbeta(-/-) mice displayed lower operant responding for ethanol and food reinforcement compared with RIIbeta(+/+) controls. However, this effect was driven by a significant increase in lever responses made by female RIIbeta(+/+) mice. When the excessive lever responses of the female RIIbeta(+/+) mice are accounted for, the RIIbeta(-/-) mice show ethanol lever responses comparable to controls. Following operant self-administration testing, RIIbeta(-/-) mice of both sexes consumed more ethanol solution compared with RIIbeta(+/+) mice during 2-bottle testing. CONCLUSIONS: Increased ingestion of ethanol by RIIbeta(-/-) mice is likely the result of altered PKA activity within neuronal pathways that control ethanol-consummatory behaviors. Conversely, the RIIbeta subunit of PKA appears not to play a critical role in neuronal pathways that regulate appetitive behaviors directed at obtaining ethanol. Finally, increased operant self-administration of food and ethanol by female wild-type mice was absent in female RIIbeta(-/-) mice, suggesting that normal PKA signaling may be part of a general, and sex-dependent, mechanism involved with reinforcement-seeking behavior.     

Evidence of immune system melatonin production by two pineal melatonin deficient mice, C57BL/6 and Swiss strains

Abstract:  We evaluated two pineal melatonin deficient mice described in the literature, i.e., C57BL/6 and Swiss mice, as animal models for studying the immunomodulatory action of melatonin. Plasma melatonin levels in C57BL/6 and Swiss strains were detectable, but lower than levels in control C3H/HENHSD mice. Since these strains are suppose to be pineal melatonin deficient an extrapineal melatonin synthesis may contribute to plasma levels. Regarding cells and tissues from the immune system, all of them were found to synthesize melatonin although at low levels. N-acetyltransferase (AANAT) mRNA was also amplified in order to analyze the alternative splicing between exons 3–4 described for pineal C57BL/6 mice which generates an inclusion of a pseudoexon of 102 bp. For the pineal gland, both the wild type and the mutant isoforms were present in all mice strains although in different proportions. We observed a predominant wild type AANAT mature RNA in thymus, spleen and bone marrow cells. Peripheral blood mononuclear cells (PBMC) culture shown an evident AANAT amplification in all strains studied. Although the bands detected were less intense in melatonin deficient mice, the amplification almost reached the control cell intensity after stimulation with phytohemaglutinin (PHA). In summary, melatonin detection and AANAT mRNA expression in inbred and outbred mice clearly indicate that different cells and tissues from the immune system are able to synthesize melatonin. Thus, the pineal defect seems not to be generalized to all tissues, suggesting that other cells may compensate the low pineal melatonin production contributing to the measurable plasma melatonin level.     

Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol

Background: Intermittent access (IA) to drugs of abuse, as opposed to continuous access, is hypothesized to induce a kindling‐type transition from moderate to escalated use, leading to dependence. Intermittent 24‐hour cycles of ethanol access and deprivation can generate high levels of voluntary ethanol drinking in rats. Methods: The current study uses C57BL/6J mice (B6) in an IA to 20% ethanol protocol to escalate ethanol drinking levels. Adult male and female B6 mice were given IA to 20% ethanol on alternating days of the week with water available ad libitum. Ethanol consumption during the initial 2 hours of access was compared with a short‐term, limited access “binge” drinking procedure, similar to drinking‐in‐the‐dark (DID). B6 mice were also assessed for ethanol dependence with handling‐induced convulsion, a reliable measure of withdrawal severity. Results: After 3 weeks, male mice given IA to ethanol achieved high stable levels of ethanol drinking in excess of 20 g/kg/24 h, reaching above 100 mg/dl blood ethanol concentrations, and showed a significantly higher ethanol preference than mice given continuous access to ethanol. Also, mice given IA drank about twice as much as DID mice in the initial 2‐hour access period. B6 mice that underwent the IA protocol for longer periods of time displayed more severe signs of alcohol withdrawal. Additionally, female B6 mice were given IA to ethanol and drank significantly more than males (ca. 30 g/kg/24 h). Discussion: The IA method in B6 mice is advantageous because it induces escalated, voluntary, and preferential per os ethanol intake, behavior that may mimic a cardinal feature of human alcohol dependence, though the exact nature and site of ethanol acting in the brain and blood as a result of IA has yet to be determined.     

Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice

BACKGROUND: The development of dependence may have significant motivational consequences regarding continued use and abuse of ethanol. We have developed a mouse model of ethanol dependence and repeated withdrawals that demonstrates sensitization of seizures and other symptoms of withdrawal. It is unclear whether such experience influences ethanol drinking behavior. The present series of experiments were designed to examine whether repeated cycles of chronic ethanol exposure and withdrawal has an impact on subsequent motivation to voluntarily self-administer ethanol. METHODS: With the use of a modified sucrose-fading procedure, adult male C57BL/6J mice were trained to drink 15% (v/v) ethanol in a limited access procedure (2 hr/day). The animals were not food or water deprived at any time during the experiments. Once stable baseline intake was established, mice were exposed to four cycles of 16 hr of ethanol vapor (or air) in inhalation chambers separated by 8-hr periods of withdrawal. At 32 hr after the last cycle of ethanol exposure, all mice were tested for ethanol intake under limited access conditions for 5 consecutive days. The animals then received a second series of chronic ethanol exposure and withdrawal followed by another 5-day test period for ethanol drinking. RESULTS: Stable daily baseline intake was established in mice that drank 15% ethanol combined with 5% sucrose (experiment 1), 15% ethanol alone (experiment 2), 5% sucrose alone (experiment 3), or 15% ethanol when presented as a choice with water (experiment 4). After repeated cycles of chronic ethanol exposure and withdrawal experience, consumption of ethanol solutions increased over baseline levels and in comparison with control (air-exposed) groups. However, sucrose consumption did not change in mice that were trained to drink 5% sucrose. The increase in ethanol consumption after chronic ethanol exposure and withdrawal experience resulted in a significant increase in resultant blood ethanol levels. CONCLUSIONS: Once the positive reinforcing properties of ethanol were established, chronic ethanol exposure and withdrawal experience resulted in a significant increase in voluntary ethanol drinking that yielded a >2-fold increase in resultant blood ethanol levels. This increase in ethanol intake occurred whether ethanol was presented in combination with sucrose, alone (unadulterated), or as a choice with tap water. Furthermore, this effect seems to be selective for ethanol in that animals that were trained to drink a sucrose solution did not exhibit a change in their intake after similar chronic ethanol exposure. As such, this model may be useful in studying the mechanisms and conditions in which chronic ethanol treatment influences motivation to resume drinking after a period of abstinence (relapse).     

UV致弱日本血吸虫尾蚴诱导C57BL/6小鼠免疫保护作用的研究

目的 研究紫外线（UV）致弱日本血吸虫尾蚴诱导C57BL／6小鼠的免疫保护作用。方法分别观察不同UV强度（300、400和500μW／cm。照射的日本血吸虫尾蚴经腹部皮肤免疫）、不同免疫剂量（8、24和300条uV致弱尾蚴经腹部皮肤免疫）、不同免疫位点（300条UV致弱尾蚴经腹部和耳廓皮肤免疫）和不同免疫次数（100条UV致弱尾蚴经腹部皮肤免疫3次）诱导C57BL／6小鼠抗血吸虫攻击感染（40条正常尾蚴经腹部皮肤感染）的保护力。同时观察免疫后小鼠的体液免疫应答变化。结果 300、400和500μW／cm。UV照射的日本血吸虫尾蚴免疫C57BI。／6小鼠诱导产生的减虫率分别为2．72％、11．37％和10．38％；8、24和300条致弱尾蚴免疫小鼠诱导产生的减虫率分别为38．67％、7．54％和16．36oA；300条致弱尾蚴经腹部和耳廓皮肤免疫诱导小鼠产生的减虫率分别为16．36％和16．14％；100条致弱尾蚴免疫3次，诱导小鼠产生减虫率为4．88％。对300条uV照射尾蚴免疫后小鼠的体液免疫应答动态观察显示，与感染对照组相比，免疫组血清中可溶性成虫抗原（SWA）和可溶性虫卵抗原（SEA）特异的IgG于免疫后2周开始升高，正常尾蚴抗原（SCA）特异的IgG于免疫1周后开始升高，SWA和SCA特异的IgG随免疫次数的增加而升高。结论 UV致弱日本血吸虫尾蚴免疫C57BL／6小鼠能诱导其产生高水平的体液免疫应答，但保护力水平较低，提示C57BL／6小鼠为对UV致弱日本血吸虫尾蚴的低应答品系。     

不同品系小鼠对卡氏肺孢子虫的易感性及其免疫反应的研究

目的　探讨不同品系小鼠对卡氏肺孢子虫 (P.c)的易感性及其免疫反应。　方法　以接触传播方式使BAL B/ c和 C5 7BL / 6小鼠 (各 15只 )感染 P.c。观察小鼠与传染源接触 4、5、6 wk后肺内虫数、支气管肺泡灌洗液中CD4 + T细胞和 CD8+ T细胞及血清 Ig G水平的变化。　结果　与传染源接触 4 wk,小鼠肺内均可检出 P.c,之后 ,BAL B/ c小鼠虫数继续增高 ,5 wk末达高峰。4 wk时 C5 7BL/ 6小鼠虫数无明显变化 ,5 wk时显著少于 BAL B/ c小鼠。两组小鼠支气管肺泡灌洗液内 CD4 + CD6 2 low T细胞和 CD8+ CD6 2 low T细胞数明显增多 ,血清 Ig G抗体水平显著上升。6 wk小鼠肺内 P.c均转阴。　结论　 BAL B/ c比 C5 7BL / 6小鼠更易感染 P.c。 BAL B/ c和 C5 7BL / 6小鼠感染 P.c后5 wk可产生有效的细胞和体液免疫反应并清除肺内感染的 P.c     

Bipedal ambulation induces experimental scoliosis in C57BL/6J mice with reduced plasma and pineal melatonin levels

In addition to the induction of scoliosis in chickens by pinealectomy (PINX), we previously demonstrated that removal of the pineal gland also produces scoliosis in bipedal rats, which can be inhibited by melatonin treatment. Using C57BL/6J mice with genetically low circulating melatonin levels, the main objective of the present study was to investigate whether bipedal ambulation in C57BL/6J mice has the same effects on spinal deformity as those seen in pinealectomized bipedal rats. The present study consisted of two phases. The aim of the first experiment was to determine whether the C57BL/6J mouse strain actually exhibits depressed plasma concentrations and/or pineal contents of melatonin during both the light and the dark phase of the light:dark cycle. The aims of the second experiment were to evaluate; (i) whether bipedal ambulation alone in the C57BL/6J mouse induces scoliosis, and (ii) whether PINX with bipedal ambulation in another mouse strain, i.e. C3H/HeJ, which normally exhibits diurnal fluctuations in melatonin synthesis and secretion, has effects similar to those of bipedal ambulation alone in C57BL/6J mice. C3H/HeJ mice, serving as controls, showed significant increases in both plasma concentrations and pineal contents of melatonin during the dark phase when compared with the light phase. In contrast, there were no differences in either circulating levels or pineal contents of melatonin between the light and dark phases in C57BL/6J mice. Moreover, plasma melatonin levels were below the detection limit of the assay in both phases and pineal melatonin was < 10% of that in C3H/HeJ mice. Bipedal ambulation for 40 wk in C57BL/6J mice induced scoliosis at a rate of 64.3%, and two of nine scoliotic mice showed two sites of spinal deformity. This type of ambulation in C3H/HeJ mice resulted in scoliosis at a lower rate (25%), and affected animals had only a single scoliotic site. However, PINX combined with bipedal ambulation in C3H/HeJ mice produced scoliosis at a rate (70%) similar to that seen in C57BL/6J mice, and some double deformations were induced. These results confirm our previous observations in rats, and also support our hypothesis that melatonin as well as the bipedal ambulation appear to play a critical pathogenic role in scoliosis in experimental mammals.