Dissociation of multiple behavioral effects between olfactory bulbectomized C57Bl/6J and DBA/2J mice

The behavioral effects of bulbectomy and subsequent antidepressant treatment in two mice strains were compared on measures of open field behavior and passive and active avoidance 2 and 4 weeks after surgery. After bulbectomy, both strains displayed elevated locomotion in open field, corrected by antidepressants. Enhanced rearing was decreased by antidepressants in C57Bl/6J, but not in DBA/2J mice. Passive avoidance, being intact 2 weeks after surgery in both strains, was strongly impaired 4 weeks after bulbectomy in C57Bl/6J mice, with antidepressants restoring the performance. Active avoidance acquisition and retention were also dramatically disturbed in C57Bl/6J mice 2 and 4 weeks after surgery, and antidepressants had recuperative effect. In contrast, bulbectomized DBA/2J mice didn't show any significant passive or active avoidance deficits, and antidepressant treatment seemed to have no effect on their learning ability. The observed strain differences suggest that bulbectomy may produce quite diverse neurophysiological and neurochemical alterations in two strains.     

Genetics ethanol and the Fos response: a comparison of the C57BL/6J and DBA/2J inbred mouse strains

The effect of ethanol (0.25 to 4 g/kg) on the number of Fos-like immunoreactive (Fos-li) neurons was studied in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. The brain regions emphasized in the analysis were from the basal ganglia and some associated limbic nuclei. The question addressed was whether or not the D2 and B6 strains differed in these regions in a way that could explain the marked psychomotor stimulation of the D2, but not the B6, strain over the dose range of 1 to 2 g/kg of ethanol. Over the dose range of 0.25 to 2 g/kg, ethanol caused a modest increase in the number of Fos-li neurons within the caudate putamen (dorsolateral and dorsomedial) and the nucleus accumbens (core and shell), but there were no marked strain effects. There was no significant effect in either strain of ethanol treatment (0.25 to 2 g/kg) in the globus pallidus, ventral pallidum, and subthalamic nucleus. However, at 4 g/kg, there was a dramatic (> 100%) increase of Fos-li neurons in the D2 but not B6 strain. A similar effect was noted in the entopeduncular nucleus, the substantia nigra zona reticulata (and compacta), but not the ventral tegmental area. A marked and substantial (> 200%) Fos response was seen in the central amygdaloid nucleus (CeA) of the D2 strain over the entire dose range; in contrast, a substantial Fos response in the B6 strain was seen only at the 4 g/kg dose. The paraventricular thalamic nucleus, in general, paralleled data in the CeA; but, the Fos response was more modest, and the results for the D2 strain were significant only at the 2 g/kg dose. Overall, data suggest that ethanol at low to moderate doses induces significant, strain-dependent Fos responses in some limbic structures, but not in the basal ganglia. The possibility is considered that activation of some neurons in the CeA are permissive for expression of the ethanol-induced increase in motor activity.     

SEE locomotor behavior test discriminates C57BL/6J and DBA/2J mouse inbred strains across laboratories and protocol conditions.

Conventional tests of behavioral phenotyping frequently have difficulties differentiating certain genotypes and replicating these differences across laboratories and protocol conditions. This study explores the hypothesis that automated tests can be designed to quantify ethologically relevant behavior patterns that more readily characterize heritable and replicable phenotypes. It used SEE (Strategy for the Exploration of Exploration) to phenotype the locomotor behavior of the C57BL/6 and DBA/2 mouse inbred strains across 3 laboratories. The 2 genotypes differed in 15 different measures of behavior, none of which had a significant genotype-laboratory interaction. Within the same laboratory, most of these differences were replicated in additional experiments despite the test photoperiod phase being changed and saline being injected. Results suggest that well-designed tests may considerably enhance replicability across laboratories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex-restricted non-Mendelian inheritance of mouse chromosome 11 in the offspring of crosses between C57BL/6J and (C57BL/6J x DBA/2J)F1 mice

We report on the observation of sex-restricted, non-Mendelian inheritance over a region of mouse Chromosome (Chr) 11, occurring in the offspring of crosses between two commonly used Mus musculus-derived inbred strains, C57BL/6J and DBA/2J. In the surviving backcross progeny of reciprocal matings between (C57BL/6J x DBA/2J)F1 hybrids and the C57BL/6J parental strain, we observed the preferential appearance of C57BL/6J alleles along a region of Chr 11. The deviation from Mendelian predictions was observed only in female offspring from both reciprocal backcrosses, and not in males from either cross. The sex-specificity of the observed non-Mendelian inheritance points to an explanation based on embryonic or neonatal lethality. Our data add to previously obtained evidence for a Chr 11 locus or loci with sex-specific and allele-specific effects on viability.     

Genetics, haloperidol, and the Fos response in the basal ganglia: a comparison of the C57BL/6J and DBA/2J inbred mouse strains

The haloperidol-induced increase of Fos-like immunoreactive (Fos-li) neurons in the basal ganglia was compared in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. The D2 strain is 10-fold more sensitive than the B6 strain to haloperidol-induced catalepsy, a putative animal model of the extrapyramidal symptoms (EPS) seen after the administration of typical neuroleptics. In contrast, the strains are equally sensitive to the haloperidol facilitation of prepulse inhibition of the acoustic startle response, a measure of drug efficacy on the mesolimbic dopamine system. The haloperidol effects on Fos-li neurons were examined over the range of 0.1 to 6.0 mg/kg; the ED50s for haloperidol-induced catalepsy are 0.4 and 3.8 mg/kg in the D2 and B6 strains, respectively. In neither the core or shell of the nucleus accumbens nor the caudate-putamen (including the dorsolateral aspect) did the D2 strain show a greater Fos response compared to the B6 strain. In fact, in the dorsolateral caudate-putamen, the B6 strain showed a modest but significantly greater Fos response. However, at the output nuclei of the basal ganglia, the entopeduncular nucleus (EP) and the substantia nigra zona reticulata (SNr), the D2 strain consistently showed a greater Fos response. These data suggest that the EP and SNr may be important to understanding the difference in haloperidol-induced catalepsy between the D2 and B6 strains.     

A major influence of sex-specific loci on alcohol preference in C57Bl/6 and DBA/2 inbred mice

C57Bl/6 mice reproducibly prefer to ingest more 10% ethanol in a two-bottle choice paradigm than do DBA/2J mice. In this paper we report the identification of two new sex-specific alcohol preference (Alcp) loci. Melo and associates (1996) identified two loci: Alcp1, a male-specific locus on Chromosome (Chr) 2, and Alcp2, a female- and cross-specific locus on Chr 11. We have additionally identified Alcp3, a male-specific locus on Chr 3, and Alcp4, a female-specific locus on Chr 1. We have also performed a statistical analysis to exclude the possibility of undiscovered major alcohol preference loci that are not sex-specific in our backcross paradigm. Our results indicate that alcohol preference in C57BL/6 mice, as measured in our backcross, is largely controlled in a sex-specific manner.     

Behavioral sensitization to drug stimulant effects in C57BL/6J and DBA/2J inbred mice.

Common features shared by addictive drugs have been difficult to identify. One ubiquitous effect of these drugs is psychomotor stimulation. Further, repeated exposure commonly results in sensitization to drug stimulant effects. This study evaluates sensitization to drugs from several drug classes in C57BL/6J and DBA/2J inbred strain mice. DBA/2J mice showed sensitized responses to ethanol and methamphetamine, whereas C57BL/6J mice developed sensitization to morphine and methamphetamine. Strain susceptibilities to ethanol- and morphine-induced sensitization closely paralleled their sensitivities to the acute stimulant effects of these drugs; this was not the case for methamphetamine. The relative sensitivities of DBA/2J and C57BL/6J mice were not consistent across drugs, suggesting that the stimulant and sensitized responses to these drugs may be mediated by at least partially divergent neural mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Genetics of ethanol-induced locomotor activation: detection of QTLs in a C57BL/6J x DBA/2J F2 intercross

Moderate doses of ethanol (1-2 g/kg) markedly increase locomotor activity in some inbred mouse strains, for example, the DBA/2J (D2), but have relatively little effect in other strains, for example, the C57BL/6J (B6). In the present study, we conducted a genome-wide search in a B6D2 F2 intercross (N = 925) for quantitative trait loci (QTLs) associated with the locomotor response. A QTL with a LOD score of 8.4 was detected on Chromosome (Chr) 2; this QTL accounted for 11.4% of the phenotypic variance and approximately 30% of the genetic variance. The QTL on Chr 2 is in the same general region as QTLs previously described for ethanol preference/consumption (Rodriguez et al. Alcohol Clin Exp Res 19, 367, 1995; Melo et al. Nat Genet 13, 147, 1996; Phillips et al. Mamm Genome, in press), acute ethanol withdrawal (Buck et al. J. Neurosci 17, 3946, 1997) and nitrous oxide withdrawal severity (Belknap et al. Behav Genet 23, 213, 1993). A logical candidate gene in the region of interest is the enzyme which synthesizes GABA, glutamic acid decarboxylase 1 (GadI).     

Ontogeny of the acoustic startle response in C57BL/6J mouse pups

A cross-sectional design was used to study the development of acoustic startle behavior in C57BL/6J mice from the approximate onset of hearing (12 days) to 17 days of age. Startle incidence and latency were recorded in response to 5-, 7-, 10-, 15-, and 20-kHz tones each presented at 80, 90, and 100 dB (SPL). From 12 to 17 days of age, higher frequency and lower intensity tones became increasingly effective in eliciting the acoustic startle response. In addition, startle latency decreased substantially, and response incidence became more sensitive to changes in tone intensity and tone frequency. This rapid ontogeny of the acoustic startle response closely parallels previously demonstrated neurophysiological development of the mouse pup auditory system.     

Developmental differences in place-learning performance between C57BL/6 and DBA/2 mice parallel the ontogeny of hippocampal protein kinase C.

This study determined the ontogenic changes in learning and hippocampal protein kinase C (PKC) in C57 and DBA mice. Mice were tested on the visible- or hidden-platform versions of the Morris water task starting at 17, 24, 31, or 60 days of age. Both strains learned to locate the visible platform at all ages. C57 mice learned to solve the hidden-platform task when they were 24 days old, whereas DBA mice never learned to solve this task. Using a [–3H]-phorbol ester binding assay, the authors found that both strains had similar amounts of hippocampal PKC at 10 and 17 days of age but that C57 mice had significantly more PKC at 24, 31, and 60 days of age. Immunoblotting results revealed that C57 mice had more γ-PKC, but not α-PKC, than DBA mice. Thus, the development of performance differences in spatial learning between C57 and DBA mice parallels the ontogeny of hippocampal PKC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: Context discrimination and the effects of retention interval.

Context discrimination and time course studies of contextual fear conditioning revealed strain differences between C57BL/6J (B6) and DBA/2J (D2) mice. Both strains discriminated contexts, but D2 mice exhibited less freezing in a shock-paired context. The strains did not differ immediately, or at 2 and 3 hr after contextual fear conditioning training. D2 mice showed less freezing at 15 min, 30 min, and 24 hr after training. B6 mice exhibited exaggerated generalized freezing and poor discrimination between the context and altered context 7-30 days after training. The acoustic startle response in B6 mice was also enhanced at 14 days after training. D2 mice did not show this pattern of generalized freezing. B6, but not D2, mice retained contextual memories for at least 60 days. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strain and sex differences on olfactory discrimination learning in C57BL/6J and DBA/2J inbred mice (Mus musculus).

In this study, the authors explored potential strain and sex differences in nonspatial cognitive ability. Beginning around 90 days of age, male and female C57BL/6J (C57) and DBA/2J (DBA) inbred mice (Mus musculus) were tested on a task of simple odor discrimination learning with 3 repeated reversals. Males learned the task more readily than females, and DBA mice learned the task more readily than C57 mice. All differences became evident after repeated testing. Similarity of perseveration measures indicated the differences were not due to inhibitory deficits. Instead, a phase analysis localized differences to a transitional period of reversal learning. Females increased transitional errors that more likely indicated adaptive sampling strategies than memory failures. C57 females used this strategy indiscriminately, but DBA females sampled as a function of environmental uncertainty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Similarities and differences in spatial learning and object recognition between young male C57Bl/6J mice and Sprague-Dawley rats.

Mice and rats are often used interchangeably in neuroscience research. However, species differences in brain structure and connectivity exist within the medial temporal lobe circuits that contribute to learning and memory. The hippocampus in particular contributes to both spatial learning and recognition memory, but the extent to which rats and mice are comparable in these two cognitive domains remains unclear. To evaluate potential species differences in spatial memory and object recognition, young adult male Sprague–Dawley rats and male C57Bl/6J mice were tested in the water maze and novel object recognition tasks. Following six days of training, with four trials per day, there was no difference in the ability of rats and mice to learn the location of a hidden platform. However, rats performed better than mice on the probe trial, indicative of superior retention. In the novel object preference test, no species differences in recognition memory were detected, although rats spent more time exploring the arena and took longer to approach the objects. These observations suggest that while species differences in spatial memory retention are present, they do not correlate with differences in object recognition memory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Histamine H? receptors mediate morphine-induced locomotor hyperactivity of the C57BL/6J mouse.

[Correction Notice: An erratum for this article was reported in Vol 100(3) of Behavioral Neuroscience (see record 2008-10953-001). An incorrect word was inadvertently printed. The last sentence of the introduction (p. 79) should read "This was accomplished by challenging the opiate-stimulated locomotion of the C57BL/6J mouse with injections of antihistamines into the nucleus accumbens/stria terminalis or lateral ventricles."] Locomotor hyperactivity induced in C57BL/6J male mice (N&=&43) by intraperitoneal morphine sulfate (30 mg/kg) was challenged with intracranial injections of antihistamines or the opiate antagonist naloxone HCl (2 μg). When 75 μg of cimetidine, an H? receptor blocker, was injected into the nucleus accumbens/stria terminalis, it significantly reduced opiate-stimulated locomotion. However, ventricular injections of cimetidine did not significantly alter hyperactivity induced by either morphine or dextroamphetamine sulfate (4 mg/kg), nor did cimetidine depress spontaneous locomotion. Although naloxone eliminated morphine-induced locomotion when injected into either the nucleus accumbens or the ventricles, chlorpheniramine (20 μg), an H? receptor blocker, failed to reduce this behavior. Data suggest that opiate-stimulated locomotion of the C57BL/6J mouse may be partially mediated by histamine H? receptors of the nucleus accumbens or closely adjacent structures. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparative genetic analysis of the role of the brain dopaminergic systems in the regulation of behavioral elements in the "open field" test in DBA/2J and C57BL/6J mice

The effects of intraperitoneal injections of sulpiride (10 mg/kg), bromocriptine (5 mg/kg), and alaptide (1 mg/kg) on the behavior of male C57BL/6J (C57BL) and DBA/2J (DBA) mice in the open-field test were studied. In this test, C57BL mice exhibited a significantly higher horizontal locomotor activity than DBA mice, whereas DBA mice moved in place substantially longer than C57BL mice. Dopaminergic agents had different effects on the open-field behavior in different mouse strains. Alaptide increased horizontal locomotor activity in DBA, but not in C57BL mice; all the three agents decreased the duration of movement in place in DBA but not in C57BL mice; bromocriptine suppressed vertical locomotor activity and the act of looking into holes in C57BL but not in DBA mice. Thus, interstrain differences in dopaminergic functions were demonstrated. The revealed strain-specific characteristics largely contribute to the determination of open-field behavior in the studied mouse strains.     

Differential effects of acrylamide on the degeneration and regeneration of myelinated fibers between C57BL/Ola and C57BL/6J mice after crush injury

Neopterin is a biochemical marker for the activation of the cell-mediated immune system. We measured neopterin, beta 2-microglobulin, and acute phase proteins in 31 HIV-seropositive and -seronegative Zambian patients with tuberculosis, using stored sera that had been obtained at the beginning and at end of antituberculosis treatment. In both HIV-seropositive and -seronegative patients neopterin and acute phase proteins were elevated when tuberculosis was initially diagnosed and fell during treatment. In contrast, the mean beta 2-microglobulin level increased during antituberculous therapy in the HIV-seropositive group. Serum neopterin levels at diagnosis were correlated with other parameters of disease activity (fever, anemia, and weight loss). In both groups, patients with persistently elevated neopterin levels at the end of treatment were more likely to suffer relapse of tuberculosis or other adverse health events in the subsequent follow-up period. Neopterin can be used to monitor the response to antituberculous therapy in both HIV-seropositive and -seronegative patients and may have a prognostic value for the patients' wellbeing in the follow-up period.     

Sodium pump distribution is not reversed in the DBA/2FG-pcy, polycystic kidney disease model mouse

Recently, it has been reported that Na,K-ATPase in the renal epithelia of human autosomal dominant polycystic kidney disease and cpk mouse, a murine model of autosomal recessive polycystic kidney disease, mislocates to apical plasma membrane and that mislocated Na,K-ATPase causes the cyst formation. Whether the DBA/2FG-pcy mice, which are presumably a suitable model for autosomal dominant polycystic kidney disease, also exhibit the reversal polarity of Na,K-ATPase localization was examined. Kidneys of newborn DBA/2FG-pcy mice, and those at early and late stages of cyst development were examined by immunohistochemical techniques. At any stage, abnormal distribution of Na,K-ATPase on the apical membranes of tubular epithelial cells could not be detected. It is suggested that cysts can be formed without reversed polarity of Na,K-ATPase distribution in pcy mice.     

Age-related association of tail tendon break time with tissue pentosidine in DBA/2 vs C57BL/6 mice: the effect of dietary restriction

In recent years, there has been a growing interest in the development of a panel of biomarkers useful in the evaluation of interventions on aging processes. An ideal marker should change with age, be related to species longevity, and respond to the effects of dietary restriction, which is the only intervention currently known to increase species longevity. In the present study; we compared parameters of collagen aging (i.e., tail tendon break time [TBT] and the glycoxidation product pentosidine) in tendon, ear, and skin of two species of rodents with different life spans: the shorter-lived DBA/2 versus the longer-lived C57BL/6 mouse strain. Both TBT and tissue pentosidine significantly increased with age in both strains of mice. The rate of increase for TBT And pentosidine occurred faster for the DBA/2 compared with the C57BL/6 strain. Dietary restriction significantly inhibited the age-related increase of TBT and pentosidine formation rte in DBA/2 mice. In C57BL/6 mice, the age-related increase of TBT was significantly inhibited by dietary restriction. However, except for tendon at 24 months, pentosidine level was not affected by dietary restriction. These studies show that the rate of collagen aging, as reflected by TBT and glycoxidation, increases proportionally with age, and that these rate increases are related to longevity in two strains of mice. Pentosidine can be monitored with age just as well in a piece of easily accessible ear tissue as in skin or tendon. Thus, pentosidine is expected to be a useful and easily measurable noninvasive marker in future intervention studies on aging.     

Differential effects of localized lesions of n. accumbens on morphine- and amphetamine-induced locomotor hyperactivity in the C57BL/6J mouse.

In 2 experiments with 46 C57BL/6J mice, it was found that Ss became hyperactive to increasing doses of morphine sulfate. This response was similar to locomotor hyperactivity induced by amphetamine. Lesions and chemical blockade of posterior nucleus accumbens abolished amphetamine-induced hyperactivity and reduced but did not abolish the morphine response. Results demonstrate that response to the drugs is mediated by overlapping but noncongruent neural systems. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)