不同品系小鼠肥胖模型比较及C57BL/6J小鼠肥胖机制研究

目的建立和比较不同品系小鼠肥胖模型,并研究C57BL/6J小鼠肥胖形成的分子机制。方法选用C57BL/6J、ICR和KM 3个品系♂小鼠,各品系小鼠随机分为正常对照和高脂模型组,分别在饲养4周与8周后测定小鼠体重、脂肪重量、Lee’s指数;脂肪细胞形态学观察和横截面面积计量;酶法检测血脂和LPL活性,应用荧光实时定量PCR技术探讨模型形成分子机制。结果 C57BL/6J小鼠模型组体重、脂肪重量、Lee’s指数、脂肪细胞横截面面积与对照组比较均明显升高,形成良好肥胖模型,而ICR和KM小鼠肥胖指标不如C57BL/6J小鼠变化明显。机制研究表明,C57BL/6J小鼠造模后血清LPL活性升高,肝脏PPARα、脂肪组织PPARγ和DGAT表达上调,脂肪组织HSL、ATGL和TGH表达下调,这些酶、受体的表达变化是形成肥胖的重要机制。结论 C57BL/6J小鼠经高脂饲料诱导4周后可形成良好肥胖模型,PPARα、PPARγ、LPL、DGAT、HSL、ATGL和TGH既是肥胖形成的主要机制,也是减肥药物作用靶点判断的生物标志物。     

Diet-induced obesity and cardiovascular regulation in C57BL/6J mice

1. In the present study, we determined the effect of diet-induced obesity on cardiovascular and metabolic regulation in mice at standard laboratory temperatures (ambient temperature (Ta) = 22 degrees C) and during exposure to thermoneutrality (Ta = 30 degrees C). 2. Male C57BL/6J (B6) mice fed a high-fat diet (HFF; n = 17) or chow (CHW; n = 14) for 15 weeks were surgically instrumented with telemetry devices, housed in metabolic chambers and assigned to either control or atenolol treatment (25 mg/kg per day in drinking water) to determine the effects of obesity on baseline cardiovascular function and on the responses to thermoneutrality and 24 h fasting. Mean arterial pressure (MAP), heart rate (HR), arterial pressure and HR variability (time and frequency domain), oxygen consumption (VO2) and locomotor activity were determined. 3. The HFF mice exhibited increased bodyweight (+10.6 +/- 4.1 g), moderate light period hypertension (+8.6 +/- 2.6 mmHg), no difference in HR and increased HR variability at standard laboratory temperature compared with CHW controls. Atenolol produced less of a decrease in HR in HFF mice (-42 +/- 10 b.p.m.) compared with CHW controls (-73 +/- 15 b.p.m.). Acute exposure to thermoneutrality (Ta = 30 degrees C) reduced HR similarly in both HFF and CHW mice (approximately 175 b.p.m.), but reduced MAP less in HFF than in CHW mice (-7.3 +/- 2.5 and -15.2 +/- 1.0 mmHg), respectively. Atenolol treatment had only minor effects on the HR response to thermonuetrality (-114 +/- 13 and -129 +/- 8 b.p.m. in HFF and CHW mice, respectively). The HFF mice displayed greater fasting-induced reductions in light period MAP than did CHW mice (-10.0 +/- 1.1 vs-3.1 +/- 3.5 mmHg, respectively), whereas HR was decreased equally in both groups. Fasting-induced increases in HR variability were attenuated in HFF mice. 4. We conclude that diet-induced obesity produced generally minor changes in cardiovascular regulation in B6 mice at baseline, some of which are distinct from the effects of diet-induced obesity in larger animal models. In contrast, acute variations in Ta or caloric availability produce pronounced alterations in cardiovascular function in either lean or obese mice, which are generally evident after atenolol and, thus, presumably not due exclusively to variation in cardiac sympathetic activity. Interestingly, the degree of obesity induced hypertension was augmented when mice were studied at thermonuetrality. The results suggest an important unrecognized role for vagal tone in the regulation of cardiovascular function in mice and support the need for considerable caution when using mouse models of obesity to examine regulation of cardiovascular function. We argue that mouse physiology studies should be performed in thermoneutral conditions.     

tert-Butylhydroquinone reduces lipid accumulation in C57BL/6 mice with lower body weight gain

tert-Butylhydroquinone (tBHQ) is a commonly used antioxidant additive that is approved for human use by both the Food and Agriculture Organization and the World Health Organization (FAO/WHO). In this study, we examined the effect of tBHQ on body weight gain and found that food supplementation with 0.001 % (w/w) tBHQ inhibited 61.4 % (P < 0.01) of body weight gain in high-fat diet (HFD)-induced C57BL/6 mice, and the oral administration of tBHQ (1.5 mg/kg) reduced 47.5 % (P < 0.05) of body weight gain in normal diet fed db/db mice. The HFD increased lipid deposit in adipocytes, but these were reduced significantly by tBHQ treatment in C57BL/6 mice. tBHQ supplementation significantly lowered the plasma triglyceride and total cholesterol, with reduced size of accumulated fat mass. The rate limiting enzyme of beta-oxidation (ACOX1) was significantly over-expressed in the liver with tBHQ treatment. These results indicate that tBHQ suppresses body weight gain in mice, possibly at least related to the up-regulation of ACOX1 gene expression.     

Effects of naloxone on ethanol induced alterations of locomotor activity in C57BL/6 mice

Ethanol (2 g or 3 g/kg) or water vehicle was injected intraperitoneally into C57BL/6 mice 15 min after injections of naloxone, a narcotic analgesic antagonist, or its saline vehicle. Locomotor activity was monitored for 60 min beginning 30 min (Experiment 1) or immediately (Experiment 2) following the ethanol injection. In both experiments, animals injected with the lower dose of ethanol were more active than controls during the second half of the activity test. Animals injected with the high dose of ethanol were less active than controls during the first half of the activity test but returned to control levels or above during the second half of the test. Naloxone at the doses used injected 45 min prior to the activity test (Experiment 1) did not alter locomotor activity and did not influence ethanol induced activity changes. When injected 15 min prior to testing (Experiment 2), however, naloxone alone produced a transient reduction in activity observed only during the first half of testing. During the second half of testing all animals injected with naloxone had activity levels similar to controls and lower than those of animals injected with ethanol in the absence of naloxone. Hence, it appears that naloxone at a dose and time period which does not alter the locomotor activity of mice is capable of blocking ethanol induced excitatory effects.     

扩增活化的淋巴细胞EAL在C57BL/6小鼠中的重复给药毒性研究

目的 对小鼠重复给予扩增活化的淋巴细胞EAL,考察其毒性反应,为临床应用提供安全性依据。方法 采用C57BL/6小鼠,设A、B两大项目组,每个大项目组均设置阴性对照组、溶媒对照组、低剂量（1.5×10⁶/只）及高剂量（1×10⁷/只）组。A项每组36只,进行常规毒性检测、血清生化测定、血液学测定、外周血T淋巴细胞亚群分布测定、大体病理学及组织病理学检查;B项每组24只,进行免疫学测定,包括γ-干扰素（IFN-γ）水平和外周血T淋巴细胞亚群分布测定。所有组别均雌雄各半,静脉注射给药,每周1次,共17次,恢复期为28 d。结果 重复给予EAL可能会使C57BL/6小鼠体质量和摄食量增加（P<0.05）。IFN-γ检测结果显示给药组动物个别时间点IFN-γ水平升高。组织病理学检查结果显示给予供试品会加重低剂量组、高剂量组动物脾脏生发中心明显及易染体巨噬细胞增多的病变程度和/或病变频度。供试品未对其他评价指标产生明显影响。结论 C57BL/6小鼠重复给予EAL,可能会引起动物体质量、摄食量的增加以及脾脏生发中心明显和易染体巨噬细胞增多,未见其他相关的毒理学反应。该结果为EAL进入临床试验奠定了基础。     

Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice

Some pharmacological studies showed that diethylcarbamazine (DEC) interferes with the arachidonic acid metabolism, acting as an anti-inflammatory drug. The chronic alcohol consumption activates the hepatic inflammatory response associated to T-cell activation and overproduction of pro-inflammatory cytokines. The present work analyzed the anti-inflammatory effect of DEC on hepatic cells of alcoholic mice. Thirty-two male C57BL/6 mice were equally divided in the following groups: (a) control group (C), which received only water, (b) DEC-treated group, which received 50 mg/kg for 12 day (DEC50), (c) the alcoholic group (EtOH), submitted to only alcohol and (d) the alcohol-DEC treated group (EtOH50), submitted to alcohol plus DEC treatment after the induction of chronic alcoholism for 5 weeks. Biochemical analyses were performed and liver fragments were processed for light microscopy, transmission electron microscopy, immunohistochemical and western blot. The level of AST increased significantly in alcoholic group whereas a significant reduction of serum AST was detected in the EtOH50 group. Histological and ultrastructural analysis of alcoholic group showed evident hepatocellular damage, which was strikingly reduced in the alcoholic DEC-treated group. Immunohistochemistry results revealed highly expression of inflammatory markers as MDA, NF-κB, TNF-α, IL-6, VCAM and ICAM by the hepatic cells of the EtOH group; however no immunoreactivity for any of these cytokines was detected after DEC treatment. Western blot analyses showed increased MCP-1 and iNOS expression in EtOH group, which was significantly inhibited by DEC treatment. According to the present results, DEC can be a potential drug for the treatment of chronic inflammation induced by chronic alcoholism.     

Cadmium‐induced microsatellite instability in the kidneys and leukocytes of C57BL/6J mice

Cadmium is a cytotoxic, carcinogenic, and mutagenic industrial product or byproduct. The correlation between metal exposure and microsatellite instability (MSI) has been reported by several groups. In the present study, 50 C57BL/6J mice at 6 weeks of age were divided into five groups and intraperitoneally injected with 0, 0.25, 0.5, 1, or 2 mg/kg cadmium chloride quaque die alterna for 4 weeks. Then, the liver, kidney, testis, leukocytes, bone marrow, and small intestine were collected from the treated mice and weighed. Portions of these tissues were fixed for further histological analysis, and the remaining tissues were subjected to genomic DNA extraction for the analysis of a panel of 42 microsatellite markers. The liver and testis weight coefficients were significantly changed in the 1 and 2 mg/kg cadmium chloride‐treated groups compared with the control group. Simultaneously, severe histopathologic changes in the liver and kidneys, along with a complete disorganization of testicular structure and obvious severe necrosis in the testes were observed in the cadmium‐treated group. The cadmium accumulated in the liver and kidneys of the mice in all cadmium‐treated groups; the tissue cadmium concentrations were significantly higher than those in the control group. After STR scanning, MSI was found at three loci (D15Mit5, D10Mit266, and DxMit172) in the kidneys and leukocytes of mice in the lower dose groups (0.25 and 0.5 mg/kg). In summary, we have successfully established a sub‐chronic cadmium exposure model and confirmed that cadmium exposure can induce MSI in mice. We also identified two loci that could be regarded as “hotspots” of microsatellite mutation in mice. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 683–692, 2015.     

Rac1 和 WAVE2 蛋白在高脂饮食 C57BL/6J 幼鼠肾小球中的表达及意义

目的 探讨 Rac1 和 WAVE2 蛋白在高脂饮食诱导的 C57BL/6J 幼鼠肾小球中的表达及意义。 方法 32 只 3 周龄雄性 C57BL/6J 幼鼠随机分为正常饮食组和高脂饮食组, 每组 16 只。 分别给予标准饲料（脂肪含量 10%）与高脂饲料（脂肪含量 60%）喂养 4 周。 HE 染色和 PAS 染色观察小鼠肾脏的病理形态学改变;应用免疫组织化学技术及蛋白免疫印迹技术检测 Rac1 和 WAVE2 蛋白的表达。 结果 与正常饮食组相比, 高脂饮食喂养的 C57BL/6J 幼鼠出现了肾小球系膜基质轻度增生以及渗出等病理改变。 同时高脂饮食组小鼠肾小球 Rac1 和 WAVE2 蛋白的表达明显增强。 结论 Rac1 和 WAVE2 蛋白可能共同参与了高脂饮食诱导的 C57BL/6J 幼鼠肾小球的损伤。     

Nicotine-produced relearning deficit in C57BL/6J and DBA/2J mice

Acute nicotine administration has been shown to influence the acquisition and retention of learning tasks. In order to investigate the many possible behavioral and pharmacological effects of nicotine, a modified 2×2 statedependent learning design was used to assess nicotine's effects on active avoidance learning. Male and female mice of the C57BL/6J (C57) and DBA/2J (DBA) inbred strains were injected with a control solution or with 0.5, 1.0, or 2.0 mg/kg nicotine 5 min before the start of training and, following a 24-h period, 5 min before retraining. Nicotine had no effect on the acquisition of the learning task but, depending on strain and sex, did have an effect on relearning. Relearning in the C57 males was unaffected by nicotine injection, whereas the most prominent effect of nicotine in the C57 females and the DBA males and females was a retrieval deficit. The prevalence of a nicotine-induced retrieval deficit in the present experiment suggests that those mechanisms underlying the retrieval of previously learned information are, in part, mediated or modulated by perturbations within nicotine-sensitive areas of the central nervous system.     

Genetic differences in intravenous cocaine self-administration between C57BL/6J and DBA/2J mice

In experiment 1, two different strains of mice [C57BL/6J (B6) and DBA/2J (D2)] were allowed to nosepoke for 5 µl intravenous (IV) infusions during 2-h daily sessions. Two nosepoke holes were available, only one of which was reinforced on an FR-3 schedule with a 10-s time-out indicated by a light inside the reinforced nosepoke hole. During the first nine sessions, infusions were saline. On subsequent sessions, mice acquired nosepoking for 0.5 mg/kg cocaine. Finally, all mice were extinguished by again receiving only saline infusions. Cocaine acted as a reinforcer in both strains. In experiment 2, different mice from the same two strains were allowed to acquire nosepoking for IV cocaine at one of three unit doses (0.5, 1.0, or 2.0 mg/kg). Although there were no effects of unit dose on rate of acquisition, B6 mice were faster in acquiring self-administration behavior than were D2 mice. Experiment 3 assessed behavior in the same mice, after acquisition had occurred. D2 mice nosepoked at a lower rate at asymptote than did B6 mice, but with a higher preference for the cocaine reinforced hole. Unit doses of cocaine were then manipulated within subjects, from 0.125 to 2.0 mg/kg per infusion. Higher doses yielded lower response rates than lower doses, both between and within subjects. Behavior in D2 mice relative to B6 mice also appeared to be shifted to the left of the dose-response curve measured within-subjects. Together, these findings indicate that although cocaine serves as a reinforcer in both strains, there are genetic differences in the pattern of cocaine self-administration between these two mouse strains.     

Exposure of C57BL/6 mice to carbon disulfide induces early lesions of atherosclerosis and enhances arterial fatty deposits induced by a high fat diet.

Even though atherosclerotic cardiovascular disease (ACVD) is the number one cause of death in the United States, the effects of environmental toxicants on this process are less well studied than the effects of chemicals on the second leading cause of death, cancer. There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) have increased rates of ACVD, and there is conflicting evidence of the atherogenic potential of CS2 from animal studies. Chemical modification, such as oxidation of low-density lipoproteins (LDL), is tightly associated with increased LDL uptake by macrophages and the development of arterial fatty streaks. CS2 has been previously demonstrated to modify several proteins in vitro including LDL, and others in vivo through derivatization and covalent cross-linking. To investigate both the capacity of CS2 to induce arterial fatty deposits by itself, and its ability to enhance the rate of fatty deposit formation induced by a western style, high fat diet, groups of 20 female C57BL/6 mice were exposed to 0, 50, 500, or 800 ppm CS2 by inhalation. Half the animals in each group were placed on an atherogenic high fat diet and half on a control diet (NIH-07). Animals were sacrificed after 1, 4, 8, 12, 16, or 20 weeks of exposure, and the rates of fatty deposit formation under the aortic valve leaflets were evaluated. Exposure of mice on the control diet to 500 and 800 ppm CS2 induced a small but significant increase in the rate of fatty deposit formation over non-exposed controls. A more striking result was observed in the animals on the high fat diet. There was marked enhancement of the rate of fatty deposit formation in mice exposed to 500 and 800 ppm over the animals on the high fat diet alone. In addition, there was a small but significant enhancement in mice exposed to 50 ppm over the rate of fatty deposit formation induced by the high fat diet alone. Analysis of erythrocyte spectrin for protein cross-linking revealed a dose-dependent formation of alpha- and beta-heterodimers in animals on both diets. These data demonstrate that CS2 is atherogenic at high concentrations, but more importantly, suggest that, in conjunction with other risk factors, CS2 at relatively low concentrations can enhance atherogenesis.     

Korean red ginseng (Panax ginseng) prevents obesity by inhibiting angiogenesis in high fat diet-induced obese C57BL/6J mice

Adipose tissue growth and development are thought to be associated with angiogenesis and extracellular matrix remodeling. Because ginseng has been shown to inhibit angiogenesis and matrix metalloproteinase (MMP) activity, we hypothesized that adipose tissue growth and obesity can be regulated by Korean ginseng (Panax ginseng C.A. Meyer). Wild-type C57BL/6J mice were fed for 8 weeks with a low fat diet, a high fat diet (HFD), or HFD supplemented with 0.5% or 5% Korean red ginseng extract. We measured body weight, adipose tissue mass, food intake, MMP activity, and the expression of genes involved in angiogenesis and MMPs. Administering ginseng to HFD-induced obese mice produced reductions in body weight and adipose tissue mass compared with untreated counterparts. Ginseng treatment decreased blood vessel density and MMP activity in adipose tissues. Ginseng also reduced mRNA levels of angiogenic factors (e.g., VEGF-A and FGF-2) and MMPs (e.g., MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (e.g., TSP-1, TIMP-1, and TIMP-2) in adipose tissues. These results demonstrate that ginseng effectively reduces adipose tissue mass and prevents obesity in diet-induced obese mice and that this process may be mediated in part through the anti-angiogenic actions of ginseng.     

Anti-diabetic effects of DA-11004, a synthetic idpc inhibitor in high fat high sucrose Diet-Fed C57BL/6J mice

DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where IC50 for IDPc is 1.49 microM. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1 hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat) were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/ kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.     

Effects of naloxone and naltrexone on locomotor activity in C57BL/6 and DBA/2 mice

Administration of naloxone or naltrexone in DBA/2 (DBA) mice was followed by dose related depressant effects. The locomotor activity of the C57BL/6 (C57) mice injected with naltrexone was also depressed. Low doses of naloxone induced a decrease in activity in the C57 strain. This effect gradually disappeared at intermediate doses and recurred again at higher doses. The results are discussed in terms of differences in type number and/or distribution of the receptors influenced by naloxone and naltrexone in the two strains of mice tested.     

Berberine inhibits dyslipidemia in C57BL/6 mice with lipopolysaccharide induced inflammation

BackgroundInhibiting the action of proprotein convertase subtilisin/kexin type 9 (PCSK9) on the low-density lipoprotein receptor (LDLR) has emerged as a novel therapeutic target for hypercholesterolemia. Here we investigated the effect of berberine, natural plant extracts, on PCSK9-LDLR pathway in C57BL/6 mice with lipopolysaccharide (LPS) induced inflammation.MethodsForty female mice were divided into four groups (n = 10): control, LPS (5 mg/kg), LPS + berberine 10 (5 mg/kg LPS plus 10 mg/kg berberine), and LPS + berberine 30 (5 mg/kg LPS plus 30 mg/kg berberine). Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; pro-inflammatory cytokines [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)], 8-isoprostane, hepatic expressions of PCSK9 and LDLR were determined.ResultsBerberine pretreatment reduced the expression of hepatic PCSK9, decreased the plasma TC, TG, LDL-C, IFNγ, TNFα, IL-1α, and 8-isoprostane concentrations; increased HDL-C level and LDLR expression in mice.ConclusionThe present results suggest that berberine inhibits dyslipidemia in C57BL/6 mice with LPS induced inflammation through regulating PCSK9-LDLR pathway.     

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

Research has suggested that chronic low‐level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low‐level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre‐adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low‐dose) or 230 ppm (high‐dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl^–1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low‐level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low‐level lead exposure. This is the first animal study to show behavioral effects in pre‐adolescent lead‐exposed mice with BLL below 5 µg dl^–1. Copyright © 2014 John Wiley & Sons, Ltd.     

Cis‐bifenthrin induces immunotoxicity in adolescent male C57BL/6 mice

Bifenthrin (BF) is an important synthetic pyrethroid. Previous studies have demonstrated that cis‐BF exhibits toxic effects on development, the neurological, reproductive and endocrine system. In this study, we evaluated the immunotoxicity caused by cis‐BF in adolescent male C57BL/6 mice. Mice were exposed orally to 0, 5, 10, and 20 mg/kg/d for 3 weeks. The results showed that body weight, spleen weight, and splenic cellularity decreased in mice exposed to 20 mg/kg/d cis‐BF. Additionally, we found that the mRNA levels of the pro‐inflammatory factors IL‐1β, IL‐6, CXCL‐1, and TNF‐α, in peritoneal macrophages, the spleen, and the thymus were inhibited in the cis‐BF‐treated groups. Moreover, MTT assays demonstrated that cis‐BF inhibited splenocyte proliferation stimulated by LPS or Con A, as well as the secretion of IFN‐γ on Con A stimulation. Collectively, the results of this study suggest that exposure to cis‐BF has the potential to induce immunotoxicity in adolescent male C57BL/6 mice.     

Pharmacogenetic differences in audiogenic seizure priming of C57BL/6Bg and DBA/1Bg-asr mice

Susceptibility to audiogenic seizures can be induced in some strains of resistant mice by exposure to an initial auditory stimulus (acoustic priming). Aminooxyacetic acid, hydrazine, glutamic acid, gamma-aminobutyric acid (GABA), cycloheximide, and metyrapone antagonize the acoustic priming of audiogenic seizure susceptibility in C57BL/6Bg mice, whereas only metyrapone attenuates that of DBA/1Bg-asr mice. The strain difference in the effect of AOAA and cycloheximide is correlated with a small, transient fall in level of brain GABA in C57BL/6Bg but not DBA/1 Bg-asr mice. These findings support our hypothesis that there are at least two neural mechanisms of acoustic priming, each with its own genetic basis and that corticosteroids are required by both mechanisms for the development of primed seizures.