Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice

Age-related changes in neurogenesis and its modulation by caloric restriction (CR) were studied in C57BL/6 mice. To this end, bromodeoxyuridine (BrdU) labeling was used to assess neuronal and glial precursor proliferation and survival in the granular cell layer (GCL) and the hilus of the dentate gyrus of 2-, 12-, 18-, and 24-month-old mice. For both regions, we found an age-dependent decrease in proliferation but not in survival of newborn cells. Interestingly, the reduction in proliferation occurred between 2 and 18 months of age with no additional decline between 18- and 24-month-old mice. Phenotyping of the newborn cells revealed a decrease in the neuron fraction in the GCL between 2 and 12 months of age but not thereafter. The majority of BrdU cells in the hilus colocalized with astrocytic but none with neuronal markers. CR from 3 to 11 months of age had no effect on neurogenesis in the GCL, but had a survival-promoting effect on newly generated glial cells in the hilus of the dentate gyrus. In conclusion, C57BL/6 mice reveal a substantial reduction in neurogenesis in the dentate gyrus until late adulthood with no further decline with aging. Long-term CR does not counteract this age-related decline in neurogenesis but promotes survival of hilar glial cells.     

Comparison of C57BL/6 and DBA/2 mice in food motivation and satiety

Demand functions describe the relationship between the consumption of a commodity and its mean or unit price. In the first experiment, we analyzed food demand in two strains of mice (C57BL/6 and DBA/2) that differ on several behavioral dimensions, but have not been examined extensively for differences in feeding and meal patterns. Mice worked for food pellets in a continuous access closed economy in which total intake and meal patterns could be measured. A series of fixed (FUP), variable (VUP), and progressive (PUP) unit price schedules were imposed. Under all schedules, DBA/2 mice consumed significantly more food than C57BL/6, a difference that was not attributable to disparity in body weight or weight gain. The higher intake of DBA/2 mice was due predominantly to larger meal size compared with C57BL/6, with no strain difference in meal frequency. In a second experiment, strain differences in meal size were not found to correlate with anorectic sensitivity to cholecystokinin (CCK) administration, or with c-Fos expression induced by CCK in PVN, AP and NTS. Thus, DBA/2 mice were motivated to sustain a higher daily food intake and meal size than C57BL/6 under the range of demand costs employed in the present work, but this strain difference is unlikely to be due to CCK action or responsiveness.     

Effect of long-term caloric restriction on oxygen consumption and body temperature in two different strains of mice

The hypothesis, that a decrease in metabolic rate mediates the life span prolonging effect of caloric restriction (CR), was tested using two strains of mice, one of which, C57BL/6, exhibits life span extension as a result of CR, while the other, DBA/2, shows little or no effect. Comparisons of the rate of resting oxygen consumption and body temperature were made between the strains after they were fed ad libitum (AL) or maintained under 40% CR, from 4 to 16 months of age. Ad libitum-fed mice of the two strains weighed the same when young and consumed similar amounts of food throughout the experiment; however, the C57BL/6 mice weighed 25% more than DBA/2 mice at 15 months of age. The rate of oxygen consumption was normalized as per gram body weight, lean body mass or organ weight as well as per animal. The body temperature and the rate of oxygen consumption, expressed according to all of the four criteria, were decreased in the DBA/2 mice following CR. The C57BL/6 mice also showed a CR-related decrease in body temperature and in the rate of oxygen consumption per animal and when normalized according to lean body mass or organ weight. The results of this study indicate that CR indeed lowers the rate of metabolism; however, this effect by CR does not necessarily entail the prolongation of the life span of mice.     

Maternal behavior in female C57BL/6J and DBA/2J inbred mice.

Inbred strains of mice exhibit different patterns of maternal behavior, providing material for studies of genetic influences on the expression of maternal behavior. Beginning 1 day after birth, maternal behavior was recorded daily for 14 days in the first and second litters of C57BL/6J (B6) and DBA/2J (D2) mothers. D2 mice had higher pup survival than B6 mice, and pup survival was higher in both strains in second litters than in first litters. D2 mothers spent more time engaged in maternal behavior, especially resting with, crouching over, and nursing pups than B6 mothers with first litters, but not with second litters. Not all measures of maternal behavior were correlated with pup survival; with both litters, B6 mothers retrieved pups faster than D2 mothers.     

Sex differences in the effect of finasteride on acute ethanol withdrawal severity in C57BL/6J and DBA/2J mice

The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of GABAA receptors that can modulate ethanol (EtOH) withdrawal. The 5alpha-reductase inhibitor finasteride can block the formation of ALLO and other GABAergic neurosteroids and also reduce certain effects of EtOH. Treatment with finasteride during chronic EtOH exposure decreased EtOH withdrawal severity and blood EtOH concentrations (BECs), suggesting an additional effect of finasteride on EtOH pharmacokinetics. Thus, the purpose of the present study was to determine the effect of finasteride on acute EtOH withdrawal severity, to minimize the effect of finasteride on EtOH metabolism. Male and female C57BL/6J and DBA/2J mice received a pretreatment of finasteride (50 mg/kg i.p.) or vehicle 24 h prior to an injection of EtOH (4 g/kg i.p.) or saline. Handling-induced convulsions (HICs) were scored at baseline, and then over a 24 h period after EtOH or saline injection. In another experiment, plasma estradiol and corticosterone levels were assessed at selected time points (0, 2, 8, and 24 h). In a final study, retro-orbital blood samples were collected at 30, 60, 120, and 240 min post-EtOH administration to access finasteride's effects on EtOH clearance parameters. Pretreatment with finasteride increased acute EtOH withdrawal severity in female C57BL/6J and DBA/2J mice but decreased withdrawal severity in male mice of both strains. Finasteride did not alter BECs, EtOH clearance, estradiol, or corticosterone concentrations in a manner that appeared to contribute to the sex difference in finasteride's effect on acute EtOH withdrawal severity. These findings suggest that male and female C57BL/6J and DBA/2J mice differ in their sensitivity to changes in ALLO or other GABAergic neurosteroid levels during acute EtOH withdrawal. Sex differences in the modulation of GABAergic 5alpha-reduced steroids may be an important consideration in understanding and developing therapeutic interventions in alcoholics.     

C57BL/6J mice exhibit reduced dopamine D3 receptor-mediated locomotor-inhibitory function relative to DBA/2J mice

Previous reports have identified greater sensitivity to the locomotor-stimulating, sensitizing, and reinforcing effects of amphetamine in inbred C57BL/6J mice relative to inbred DBA/2J mice. The dopamine D3 receptor (D3R) plays an inhibitory role in the regulation of rodent locomotor activity, and exerts inhibitory opposition to D1 receptor (D1R)-mediated signaling. Based on these observations, we investigated D3R expression and D3R-mediated locomotor-inhibitory function, as well as D1R binding and D1R-mediated locomotor-stimulating function, in C57BL/6J and DBA/2J mice. C57BL/6J mice exhibited lower D3R binding density (-32%) in the ventral striatum (nucleus accumbens/islands of Calleja), lower D3R mRNA expression (-26%) in the substantia nigra/ventral tegmentum, and greater D3R mRNA expression (+40%) in the hippocampus, relative to DBA/2J mice. There were no strain differences in DR3 mRNA expression in the ventral striatum or prefrontal cortex, nor were there differences in D1R binding in the ventral striatum. Behaviorally, C57BL/6J mice were less sensitive to the locomotor-inhibitory effect of the D3R agonist PD128907 (10 microg/kg), and more sensitive to the locomotor-stimulating effects of novelty, amphetamine (1 mg/kg), and the D1R-like agonist +/- -1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8,-diol hydrochloride (SKF38393) (5-20 mg/kg) than DBA/2J mice. While the selective D3R antagonist N-(4-[4-{2,3-dichlorphenyl}-1 piperazinyl]butyl)-2-fluorenylcarboxamide (NGB 2904) (0.01-1.0 mg/kg) augmented novelty-, amphetamine-, and SKF38393-induced locomotor activity in DBA/2J mice, it reduced novelty-induced locomotor activity in C57BL/6J mice. Collectively, these results demonstrate that C57BL/6J mice exhibit less D3R-mediated inhibitory function relative to DBA/2J mice, and suggest that reduced D3R-mediated inhibitory function may contribute to heightened sensitivity to the locomotor-stimulating effects of amphetamine in the C57BL/6J mouse strain. Furthermore, these data demonstrate that comparisons between C57BL/6J and DBA/2J mouse strains provide a model for elucidating the molecular determinants of genetic influence on D3R function.     

Taste reactivity and its modulation by morphine and methamphetamine in C57BL/6 and DBA/2 mice

C57BL/6J (B6) and DBA2/J (D2) mice differ markedly in voluntary consumption of tastants and responses to abused drugs. In particular, compared to D2 mice, B6 mice avidly drink ethanol and sucrose solutions, but avoid quinine solutions. In the first study, we compared taste reactivity in B6 and D2 mice to determine the extent to which differences in drinking patterns depend on orosensory processing. Both strains showed concentration-dependent increases in positive reactions to sucrose (0.01 to 1 M). Quinine (0.03 to 3 mM) elicited concentration-dependent aversive reactions in B6 mice, whereas all reactions to quinine were virtually indistinguishable from reactions to water in D2 mice. In contrast, D2 mice reacted with relatively strong aversive responses to ethanol (5 to 30%). In the second study, we evaluated the effect of subcutaneous morphine (1 to 4 mg/kg) and methamphetamine (0.5 to 2 mg/kg) on taste reactivity to sucrose. Morphine generally decreased reactions to sucrose in both strains, suggesting a general motor depressant effect. Methamphetamine shifted sucrose responses towards aversion in both strains; particularly in D2 mice. These results suggest that strain-dependent differences in voluntary ethanol and quinine drinking depend at least partially on differences in orosensory responses. However, differences in voluntary sucrose intake may relate solely to genetic differences in post-ingestive factors. Finally, as has been suggested by previous place conditioning studies, methamphetamine appears to induce a dysphoric state in D2 mice, which may be reflected in fewer positive and more negative taste reactions to sucrose in the current study.     

Differential neurosensitivity to three alcohols and phenobarbital in C57BL/6J and DBA/2J mice

Neurosensitivity to ethanol, t-butanol, 1,2-propranediol, and phenobarbital was assessed in C57BL/6J and DBA/2J mice by means of the grid test, a measure of drug-induced ambulatory ataxia. In addition, blood and brain alcohol concentrations at the time of regaining the righting reflex were determined for ethanol and t-butanol. C57BL/6J mice were consistently more neurosensitive than DBA/2J mice to all four drugs on these two tests, but no strain difference was seen with regard to alcohol-induced hypothermia. These findings, and others reported in the literature, indicate that the strain differences in neurosensitivity are very much task dependent in that some measures yield no differences while other measures produce large differences between these two strains. Thus, one strain is not uniformly more sensitive to ethanol than the other across all measures.     

Involvement of protein tyrosine phosphatases and inflammation in hypothalamic insulin resistance associated with ageing: effect of caloric restriction

Aged Wistar rats present central insulin resistance associated with ageing. Several steps of the insulin signaling pathway have been described to be impaired in aged rats at hypothalamic level. In the present article we have explored possible alterations in protein tyrosine phosphatases (PTPs) involved in insulin receptor dephosphorylation, as well as pro-inflammatory pathways and serine kinases such as inhibitory kappa β kinase-nuclear factor kappa-B (IKKβ-NFκB), p38 mitogen-activated protein kinase (p38) and protein kinase C θ (PKCθ) that may also be involved in the decreased insulin signaling during ageing. We detected that ageing brings about a specific increase in insulin receptor tyrosine phosphatase activity and PTP1B serine phosphorylation. Increased association of PTP1B and leukocyte common antigen-related tyrosine protein phosphatase (LAR) with insulin receptor was also observed in hypothalamus from aged rats. Besides these mechanisms, increased activation of the IKKβ-NFκB pathway, p38 and PKCθ serine/threonine kinases were also detected. These data contribute to explain the hypothalamic insulin resistance associated with ageing. Caloric restriction ameliorates most of the effects of ageing on the above mentioned increases in PTPs and serine/threonine kinases activities and points to age-associated adiposity and inflammation as key factors in the development of age-associated insulin resistance.     

IGF-1 as selected growth factor multi-response to antidepressant-like substances activity in C57BL/6J mouse testis model

Insulin-like growth factor (IGF-1) affects almost all cells in the body. Extremely important functions of this growth factor have been demonstrated in the brain and the reproductive system of both, females and males. Also, it is considered as a pro-inflammatory cytokine adjusting tissue homeostasis. However, it seems to play a special role in the male reproductive system and it may be disturbed by the application of antidepressants with different mechanisms of drug action during therapy. To date, the effect of antidepressant-like substances (ALS) on the course of physiological processes in male testicular cells is poorly understood. Therefore, the purpose of the research was to determine the presence, localizationof IGF-1R (insulin-like growth factor 1 β receptor) and mRNA gene expression of IGF-1R and IGF-1 after administration of 3-[(2-methyl-1,3-tiazol-4-yl)ethynyl]-pyridine (MTEP) and N-[2-(Cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) in the different scheme in the testis of mice. Imipramine was used as a reference drug having a documented interaction with the mGluR5 receptors. The immunohistochemical analyses showed the localization of IGF-1R in Sertoli, Leydig, and germinal cells after all used substances. Differences in receptor localization were observed depending on the drugs applied and the type of analyzed cells. In contrast, there was a significant increase in IGF-1 gene expression after IMI + NS-398 and in IGF-1R after MTEP + NS-398 and IMI + NS-398 administration. It can, therefore, be assumed that the use of a combination of NS-398 with some ALS may run different mechanisms of action and affect the regulation of reproductive function in mouse testis through maintaining homeostasis at the molecular and immunological levels related to IGF.     

Regulation of caloric intake in yellow mice (C57BL/6J-Ay/alpha).

The ability of yellow and normal black mice to reduce food intake when given surplus calories was studied to elucidate the mechanisms responsible for hyperphagia in yellow mice. When given sugar solutions to drink, immature (6–7 weeks old) yellow mice increased total caloric intake more than did lean control mice. Older (11–14 weeks) yellow mice were similar to control mice. The oldest yellow mice tested (25–33 weeks) increased total caloric intake less than lean control mice, when given sugar solutions. In contrast, yellow mice of all ages increased total caloric intake more than lean mice when given corn oil. Yellow mice had similar or lower preference for sugar and oil calories than did black mice.     

Acute restraint stress reduces protein kinase C gamma in the hippocampus of C57BL/6 but not DBA/2 mice

Protein kinase C gamma (PKC gamma) is highly expressed in the rodent hippocampus and has been implicated in long-term alterations in synaptic efficacy. Acute stress has been shown to negatively affect hippocampal synaptic plasticity, and the present study examined the effect of acute stress on PKC gamma expression/subcellular distribution by quantitative western blotting in two inbred mouse strains (C57BL/6J versus DBA/2J) with established differences in hippocampal plasticity. It was found that both DBA/2J and C57BL/6J strains exhibited similar basal, stress-induced elevations, and recovery of serum corticosterone levels. Acute stress produced a significant reduction in both membrane and cytosolic PKC gamma expression in the hippocampus of C57BL/6J mice compared to no-stress controls, but did not alter either membrane or cytosolic PKC gamma expression in the hippocampus of DBA/2J mice compared to no-stress controls. These data provide direct evidence that PKC gamma is differentially regulated in the hippocampus of C57BL/6J and DBA/2J mice by acute stress. The role of stress-induced regulation of hippocampal PKC gamma expression in hippocampal synaptic plasticity is discussed.     

Dietary restriction increases skeletal muscle mitochondrial respiration but not mitochondrial content in C57BL/6 mice

Dietary restriction (DR) is suggested to induce mitochondrial biogenesis, although recently this has been challenged. Here we determined the impact of 1, 9 and 18 months of 30% DR in male C57BL/6 mice on key mitochondrial factors and on mitochondrial function in skeletal muscle, relative to age-matched ad libitum (AL) controls. We examined proteins and mRNAs associated with mitochondrial biogenesis and measured mitochondrial respiration in permeabilised myofibres using high resolution respirometry. 30% DR, irrespective of duration, had no effect on citrate synthase activity. In contrast, total and nuclear protein levels of PGC-1α, mRNA levels of several mitochondrial associated proteins (Pgc-1α, Nrf1, Core 1, Cox IV, Atps) and cytochrome c oxidase content were increased in skeletal muscle of DR mice. Furthermore, a range of mitochondrial respiration rates were increased significantly by DR, with DR partially attenuating the age-related decline in respiration observed in AL controls. Therefore, DR did not increase mitochondrial content, as determined by citrate synthase, in mouse skeletal muscle. However, it did induce a PGC-1α adaptive response and increased mitochondrial respiration. Thus, we suggest that a functionally ‘efficient’ mitochondrial electron transport chain may be a critical mechanism underlying DR, rather than any net increase in mitochondrial content per se.     

Preabsorptive vs. postabsorptive control of ethanol intake in C57BL/6J and DBA/2J mice

Experimentally naive male mice of both strains were exposed to a two-bottle choice situation (ethanol vs. water) and their drinking behavior was observed during the first hour. DBA/2J mice developed a significant avoidance of 2% or 10% ethanol during the first 10 min. At 15 and 60 min following introduction of the bottles, no DBA mouse exhibited more than a 6 mg % blood ethanol level while all of the C57BL mice exceeded this concentration. Significant postabsorptive effects in the DBA mice seem unlikely at these very low blood ethanol values. Animals of both strains were examined for their ability to form lithium-induced conditioned taste aversions to 2% ethanol or 15% sucrose solutions. DBA mice readily formed conditioned aversions to both solutions, but the C57BL strain significantly avoided only the sucrose. C57BL mice appear to have difficulty in discriminating the 2% ethanol from distilled water. The neural sensitivity to ethanol was examined in both strains using the sleep time test and the grid test. C57BL mice were significantly more sensitive than DBA mice in both tests.     

谷氨酰胺对高脂饮食诱导C57BL/6J小鼠肥胖和胰岛素抵抗的影响

目的:探讨谷氨酰胺(L-glutamine,Gln)对高脂饮食(high-fat diet,HFD)诱导小鼠肥胖和胰岛素抵抗的影响。方法:60只雄性C57BL/6J小鼠随机分为正常对照(normal control,NC)组、HFD组、HFD+丙氨酸(Lalanine,Ala)组和HFD+Gln组,每组15只。每周记录小鼠体重,给药16周后禁食不禁水12 h测定空腹血糖(fasting blood glucose,FBG),处死后剖腹取附睾脂肪垫并称重。采用酶联免疫法检测小鼠胰岛素(insulin,INS)、瘦素(leptin,LEP)、脂联素(adiponectin,APN)和胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)的水平,并计算胰岛素抵抗指数(insulin resistance index,IRI)和胰岛素敏感指数(insulin sensitivity index,ISI)。结果:与NC组比较,HFD组小鼠体重和附睾脂肪垫重量明显升高,FBG、INS、IRI和LEP水平均明显升高,ISI和APN水平明显降低(P0.05);与HFD组比较,HFD+Gln组小鼠体重明显下降,FBG和LEP水平明显降低,IRI明显减小(P0.05)。4组小鼠血清的GLP-1水平差异无统计学显著性。结论:谷氨酰胺减轻高脂饮食诱导的肥胖小鼠体重和胰岛素抵抗。     

热量限制改善早期社会隔离诱导的小鼠认知功能障碍

目的 探讨热量限制（CR）对早期社会隔离（SI）诱导的认知功能障碍的改善作用及其可能机制。 方法 3周龄昆明雄小鼠36只随机分成正常群居组（GH, n=12）、早期社会隔离组（SI, n=12）、热量限制干预组（SI+CR, n=12）。在相同条件下饲养GH组（6只/笼）和SI组（1只/笼）,而 SI + CR 组（1只/笼）每隔1 d给予食物。采用旷场实验检测小鼠的活动度,新旧事物识别实验检测小鼠认知功能;免疫组织化学方法检测小鼠海马区小胶质细胞标记物离子钙结合接头分子1（IBA-1）的表达;Western blotting方法检测海马组织小胶质细胞激活标记物CD68及炎症因子白细胞介素-1β（IL-1β）的表达。 结果 在旷场实验中,3组小鼠的活动度无差异。 在新旧事物识别实验中,与GH组相比,SI组新事物分辨率明显下降（P<0.01）,海马中IL-1β的表达显著上调（P<0.01）,此外,SI组在海马中表现出过度活化的小胶质细胞,表现为IBA-1阳性细胞数量增加,CD68高表达（P<0.01）;与SI组相比,SI+CR组新事物分辨率显著增加（P<0.01）,海马IL-1β的表达下调（P<0.01）,IBA-1阳性细胞的数量和CD68的表达显著减少（P<0.01）。 结论 热量限制可缓解早期社会隔离诱导小鼠的认知功能损伤,其机制可能与抑制小胶质细胞的激活及炎症因子的释放有关。     

Delayed toxicity of cyclophosphamide on the bladder of DBA/2 and C57BL/6 female mouse

The present study describes the delayed development of a severe bladder pathology in a susceptible strain of mice (DBA/2) but not in a resistant strain (C57BL/6) when both were treated with a single 300 mg/kg dose of cyclophosphamide (CY). Inbred DBA/2 and C57BL/6 female mice were injected with CY, and the effect of the drug on the bladder was assessed during 100 days by light microscopy using different staining procedures, and after 30 days by conventional electron microscopy. Early CY toxicity caused a typical haemorrhagic cystitis in both strains that was completely repaired in about 7-10 days. After 30 days of CY injection ulcerous and non-ulcerous forms of chronic cystitis appeared in 86% of DBA/2 mice but only in 4% of C57BL/6 mice. Delayed cystitis was characterized by infiltration and transepithelial passage into the lumen of inflammatory cells and by frequent exfoliation of the urothelium. Mast cells appeared in the connective and muscular layers of the bladder at a much higher number in DBA/2 mice than in C57BL/6 mice or untreated controls. Electron microscopy disclosed the absence of the typical discoidal vesicles normally present in the cytoplasm of surface cells. Instead, numerous abnormal vesicles containing one or several dark granules were observed in the cytoplasm of cells from all the epithelial layers. Delayed cystitis still persisted in DBA/2 mice 100 days after treatment. These results indicate that delayed toxicity of CY in female DBA/2 mice causes a bladder pathology that is not observed in C57BL/6 mice. This pathology resembles interstitial cystitis in humans and could perhaps be used as an animal model for studies on the disease.     

Age-related changes in visual acuity, learning and memory in C57BL/6J and DBA/2J mice

The DBA/2J mouse is a model of age-related pigmentary glaucoma in humans. Visual detection, pattern discrimination and visual acuity were evaluated in DBA/2J, C57BL/6J, B6.mpc1d (a C57 congenic strain) and D2.mpc1b (a D2 congenic strain) mice at 6, 12, 18 and 24 months of age. Mice were also tested in the Morris Water Maze and olfactory discrimination learning task. At 6 months, DBA/2J and D2.mpc1b mice outperformed C57BL/6J and B6.mpc1d mice in the visual detection task and there were no strain differences in performance on the water maze. At 12, 18 and 24 months, C57BL/6J and B6.mpc1d mice outperformed DBA/2J and D2.mpc1b mice in the vision tasks and in the water maze. Strains did not differ in the olfactory learning task. Therefore, loss of visual function occurs between 6 and 12 months of age in DBA/2J mice. Strain differences in visual task performance accounted for a significant proportion of the variance in measures of learning and memory in the water maze at 12, 18 and 24 months of age.     

Expression of the insulin-responsive glucose transporter isoform 4 in blastocysts of C57/BL6 mice

Glucose is the most important energy substrate for mammalian blastocysts. In preimplantation embryos glucose uptake is mainly mediated by facilitative glucose transporter molecules (GLUT). Employing RT-PCR in 3.5-day-old mouse blastocysts of strain C57/BL6 we have investigated the expression of the GLUT isoforms 1–4 and 8. We could not only detect GLUT 1, 3 and 8 but, in contrast to earlier studies, also the insulin-responsive isoform 4. GLUT2 was not expressed. The specificity for GLUT4 amplification was verified by sequence analysis. GLUT4 protein was localized by immunohistochemistry with two GLUT4 antibodies. It was found in ICM and trophoblast cells in the cytoplasmic compartment with a strong perinuclear staining. This is the first report on the expression of the insulin-sensitive GLUT4 isoform in mouse preimplantation embryos.Abbreviations GLUT Glucose transporter - ICM Inner cell mass - TE Trophectoderm     

Delay discounting in C57BL/6J and DBA/2J mice: adolescent-limited and life-persistent patterns of impulsivity

Impulsivity is a defining characteristic of adolescence. Compared to adults, for example, adolescents engage in higher rates of drug and alcohol experimentation, risky sexual practices, and criminal activity. Such behavior may reflect reduced sensitivity to long-term consequences of behavior during adolescence. Recently, our lab has attempted to refine mouse procedures to study developmental trends in decision making in the laboratory. In the present experiment, we examined sensitivity to delayed rewards in C57BL/6J (B6) and DBA/2J (D2) mice during adolescence and adulthood using an adaptation of a 2-week delay discounting procedure developed by Adriani and Laviola (2003). During training, mice could choose between a 20- or 100-μl drop of milk delivered after a 1-s delay. During testing, the delay to the large drop of milk was increased from 1 to 100 seconds. As the delay to the larger volume increased, preference shifted to the smaller, more immediate option. In adolescence, both strains showed similar shifts in preference. In contrast, adult B6 mice were less sensitive to increasing delays than were adult D2 mice, who continued to perform much as their adolescent counterparts. A subsequent resistance-to-extinction test ruled out the possibility that the slower change in the adult B6 mice was due to perseverative responding. The present findings suggest that B6 and D2 strains may be differentially suited to uncovering the biological mechanism of short-term and long-term patterns of impulsive behavior.