Exploration and risk assessment in female wild house mice (Mus musculus musculus) and two laboratory strains

In an evolutionary prospective, it is possible that female mice have a differential perception of novel events than male mice and use a different behavioural strategy for risk assessment. However, female mice are less studied than male mice in behavioural tests of emotional reactivity. The aim of the present study was to investigate how wild-derived female house mice differ from domesticated female mice in their risk assessment strategy. A total of 46 adult female mice, 14 BALB/c, 16 C57BL/6 and 14 Wild mice were tested in the Concentric Square Field (CSF), Open Field (OF) and Elevated Plus Maze (EPM) at three consecutive days. Parameters from all three tests were categorized according to their relevance to activity, exploration, approach-avoidance and use of open areas-shelter. Principal Component Analysis (PCA-SIMCA) of the animals' behaviour in the CSF arena was performed both for females alone and in comparison with earlier findings in male mice under the same test conditions. The results clearly show that female wild mice had a higher avoidance of open areas than the laboratory strains. There was also a trend indicating differences in exploration and approach-avoidance between female Wild and the laboratory strains. The multivariate test, CSF, was able to detect differences between Wild and laboratory strains in three (exploration, approach-avoidance, open-shelter) of the four functional categories measured. Wild female mice also had a higher frequency of rearing and grooming and a lower duration in the corridors in the CSF. Clear strain differences were found between BALB and C57BL in all tests where BALB generally had higher risk assessment and lower risk taking than C57BL. No general sex differences were found, however the sex differences were greater in Wild mice compared to the laboratory strains.     

Home cage activity and activity-based measures of anxiety in 129P3/J, 129X1/SvJ and C57BL/6J mice

We investigated the home cage activity and emotional behavior in mouse strains used as background for many studies of altered genes [C57BL/6J (B6, n=20), 129X1/SvJ (X1, n=20) and 129P3/J (P3, n=19)]. In their home cages, X1 and P3 mice exhibited less locomotion than did B6 mice, and the X1 mice showed significantly greater rearing than B6 and P3 mice did. A battery of three tests conducted in an open field (open field, emergence and novel object) revealed strain rankings of B6>X1>P3 or B6>X1=P3 in most activity variables. Significant correlations were found between home cage activity and activity in each of three tests, but not in all observation periods. Strain rankings on the elevated zero maze test were B6=X1>P3 in the number of stretched-attend body postures (SAPS) during the initial 6-min exposure for naive mice. Naive and nonnaive mice showed significantly different behaviors on the elevated zero maze. The results suggest that rankings on anxiety are P3>X1>B6 and that B6 mice have greater exploration in a novel environment compared with X1 and P3 mice. However, anxiety-like behaviors differed among strains in open-field-based tests and in the zero maze, and testing experience impacted performance on the zero maze. The findings illustrate that test variations and experience can influence performance and suggest the need for the consideration of how these factors interact with background strains in assessing gene-altered mice.     

Exploration and risk assessment: a comparative study of male house mice (Mus musculus musculus) and two laboratory strains

The ability to gather information and assess risks in novel environments is crucial for survival and fitness in the wild. Our aim was to characterise behavioural strategies of exploration and risk assessment in novel environments and to investigate in what respects wild house mice differ from domesticated mice. A total of 39 adult male mice from three genetic backgrounds (Wild, BALB/c, and C57BL/6) were tested in three behavioural tests, the concentric square field (CSF), a modified open field (OF), and a conventional elevated plus maze (EPM). In addition to spatial measures, behavioural measures of exploration and risk assessment were registered. The parameters were categorised according to their relevance to activity, exploration, approach-avoidance, and use of open areas/shelter. Wild mice had lower activity and a higher avoidance of open areas than the laboratory strains. No differences were found in exploratory motivation. The BALB/c mice avoided risk areas and showed high risk assessment (SAP), whereas C57BL/6 mice were more explorative and risk taking and showed little risk assessment. Wild mice seemed to have a different behavioural strategy of risk assessment in being more cautious before entering a potentially dangerous zone but explored all zones after assessed as nonrisky. A principal component analysis (PCA) of the animals' behaviour in the CSF arena supported these findings by clearly separating the three strains on the basis of their behavioural performances. It is concluded that there are obvious differences in behavioural strategies related to risk assessment and risk taking among wild mice versus domesticated house mice and also among laboratory strains. The relationship between the animal's risk concern and adaptability is discussed and should be a matter of importance considering animal welfare as well as the experimental aim and protocol.     

Contrasting phenotypes of C57BL/6JOlaHsd, 129S2/SvHsd and 129/SvEv mice in two exploration-based tests of anxiety-related behaviour

Knockout mice are typically generated on a mixed genetic background and, as such, detailed behavioural characterisation of these background strains is essential to the valid interpretation of mutant phenotypes. In this context, recent research has revealed significant differences in anxiety-like behaviour among the most commonly used background strains (C57BL/6J and various 129 substrains), leading to the possibility that at least certain mutant phenotypes may not after all be due to the targeted mutation. However, these findings derive largely from behavioural test batteries in which there may well be an experiential confound, while the widely reported hypolocomotor profile of most 129 substrains may compromise the principal indices of anxiety-like behaviour. In the present study, we have compared the behavioural profiles of three commonly used background strains (C57BL/6JOlaHsd, 129/SvEv and 129S2/SvHsd) in two of the most popular animal models of anxiety-the elevated plus-maze (EPM) and light/dark exploration (LDE) tests. Naive animals were used for each procedure, ethological scoring methods were employed throughout, and the inbred phenotypes were also compared with that of an outbred strain (Swiss-Webster) widely employed in test validation and behavioural pharmacology. Our results show that, despite their hypolocomotor profile, both 129 substrains display higher levels of anxiety-like behaviour (conventional and/or ethological measures) relative to the C57BL/6JOlaHsd strain. Furthermore, all three inbred strains were less active in both tests when compared with the outbred Swiss-Webster strain. However, whereas C57BL/6JOlaHsd mice displayed lower levels of anxiety-like behaviour than their Swiss-Webster counterparts (both tests), 129S2/SvHsd (but not 129/SvEv) mice exhibited evidence of higher anxiety, particularly in the LDE test. The implications of these findings are discussed in relation to both the behavioural and pharmacological phenotyping of mutant mice.     

Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies

The present study was aimed at establishing behavioral differences between three inbred mouse strains (129S2/SvHsd, C57BL/6JOlaHsd, FVB/NHsd) and two F1 hybrid lines derived from them (129 x C57BL/6 and 129 x FVB). The choice of the given strains was based on the frequent use of these mice in transgenic research. For the behavioral phenotyping, we employed a test battery consisting of the following models: elevated plus-maze (EPM), open field (OF), light-dark exploration, spontaneous locomotor activity, rota-rod (RR), Porsolt's forced-swimming test (FST), and Morris water task. Significant variations between the strains were established in all tests. Anxiety-like behavior was more pronounced in the 129S2/Sv and 129 x C57BL/6 mice, the FVB/N mice were spontaneously hyperactive, the best coordination ability was demonstrated by the C57BL/6 and 129 x C57BL/6 groups. A good performance in the learning test was established in both hybrid lines and the 129S2/Sv mice, whereas the well-known visual impairment of the FVB strain was confirmed by low performance in spatial and non-spatial tasks. Differences related to the gender were revealed occasionally; most importantly, 129 x C57BL/6 males had a higher anxiety level than their female counterparts in the EPM. Several other gender dissociations suggest the strain and task specificity. In conclusion, we would like to highlight the importance of the genetic background and gender of mice for the molecular biological and pharmacological studies and also the need for well-established testing protocols to obtain wide information at the first stage of behavioral screening of genetically modified mice.     

Genetic and pharmacological manipulation of mu opioid receptors in mice reveals a differential effect on behavioral sensitization to cocaine

Cocaine-induced behavioral sensitization is a complex phenomenon involving a number of neuromodulator and neurotransmitter systems. To specifically investigate the role of the micro opioid receptor (MOR) in cocaine-induced behavioral sensitization in mice, both genetic and pharmacological approaches were undertaken. MOR-1 deficient mice of varying backgrounds (C57BL/6J, 129S6, F1 hybrid 129S6xC57BL/6J and 129S6xC57BL/6J) and wild-type C57BL/6J mice exposed continuously to naltrexone, an opioid receptor antagonist, received single daily injections of saline or cocaine for 10 days. All mice received a single cocaine challenge 7 days following the last saline or cocaine injection to test for the expression of sensitization. The locomotor-stimulating and sensitizing effects of cocaine observed in MOR-1 wild-type mice were absent in MOR-1 knockout mice maintained on the mixed 129S6xC57BL/6J background. In contrast, MOR-1 deficient mice developed on a C57BL/6J background showed an accentuated sensitivity to cocaine-induced locomotion. Cocaine's psychomotor activating effects were more pronounced in the MOR-1 C57BL/6J knockouts injected daily with cocaine than in the MOR-1 wild-type mice. Similar locomotor-stimulating and sensitizing effects were found in both F1 hybrid 129S6xC57BL/6J MOR-1 wild-type and MOR-1 knockout mice, while the 129S6 strain showed an overall indifference to cocaine. That is, both the locomotor-stimulating and sensitizing effects of cocaine were absent in both MOR-1 wild-type and MOR-1 knockout mice maintained on the 129S6 background. Lastly, the locomotor-stimulating and sensitizing effects of cocaine were attenuated in C57BL/6J wild-type mice exposed continuously to naltrexone. Collectively, these data support a role for opioidergic involvement in cocaine-influenced behavior in mice. Moreover, MORs appear to differentially modulate a sensitized response to cocaine in different strains of mice as delineated by MOR-1 gene deletion and pharmacological antagonism.     

The use of behavioral test batteries: effects of training history

Our laboratory uses a specific test battery for the initial assessment of phenotypic behavioral differences of transgenic, knockout, and inbred strains of mice. Our standard battery includes: open field activity, light-dark exploration, rotarod, prepulse inhibition (PPI), acoustic startle habituation, conditioned fear, Morris water maze, and hot plate. Tests are run in the order listed, from least invasive to most invasive, to decrease the chance that behavioral responses are altered by prior test history. The studies presented here were designed around two questions. The first study asks if differences exist between mice that have undergone testing on different tasks and mice that are na?ve to the test experience. The second study asks if the test order affects how an animal performs on subsequent tests. In the first experiment, C57BL/6J male mice were evaluated on all of the tests described above. The behavior of these 'test battery' mice was compared to aged matched na?ve mice that were only tested on one test from the battery. Results indicate that on some tests, the behavior of 'test battery' mice was significantly different from the behavior of na?ve mice, while on other tests there were no differences. For example, test battery mice responded differently in the open-field, rotarod, and hot-plate test, but behaved similar on the PPI and conditioned fear. Experiments in the second study were performed on male 129/SvEvTac (129S6) and C57BL/6J male mice. An abbreviated battery of tasks was used and the results suggest that certain test variables are sensitive to test order, whereas others are resistant. These two studies demonstrate that some behavioral tests appear to be sensitive to previous testing experience, while other tests are immune.     

Chromosomal Assignment of Quantitative Trait Loci Influencing Modified Hole Board Behavior in Laboratory Mice using Consomic Strains,with Special Reference to Anxiety-related Behavior and Mouse Chromosome 19

Male mice from a panel of chromosome substitution strains (CSS, also called consomic strains or lines)—in which a single full-length chromosome from the A/J inbred strain has been transferred onto the genetic background of the C57BL/6J inbred strain—and the parental strains were examined in the modified hole board test. This behavioral test allows to assess for a variety of different motivational systems in parallel (i.e. anxiety, risk assessment, exploration, memory, locomotion, and arousal). Such an approach is essential for behavioral characterization since the motivational system of interest is strongly influenced by other behavioral systems. Both univariate and bivariate analyses, as well as a factor analysis, were performed. The C57BL/6J and A/J mouse parental inbred strains differed in all motivational systems. The chromosome substitution strain survey indicated that nearly all mouse chromosomes (with the exception of chromosome 2) each contain at least one quantitative trait locus (QTL) that is involved in modified hole board behavior. The results agreed well with previous reports of QTLs for anxiety-related behavior using the A/J and C57BL/6J as parental strains. The present study confirmed that mouse chromosomes 5, 8, 10, 15, 18 and 19 likely contain at least one anxiety QTL. There was also evidence for a novel anxiety QTL on the Y chromosome. With respect to anxiety-related avoidance behavior towards an unprotected area, we have special interest for mouse chromosome 19. CSS-19 (C57BL/6J-Chr19^A/NaJ) differed in avoidance behavior from the C57BL/6J, but not in locomotion. Thus pleiotropic contribution of locomotion could be excluded. Edited by Pierre Roubertoux.     

Differential effects of age on motor performance in two mouse strains

The performance of male A/J and C57BL/6J mice from three age groups (4, 18, and 24 months) was observed in a battery of tests designed to assess age-related impairments in motor abilities. A/J mice were superior to C57BL/6J mice in tasks requiring upper body strength, such as tests of grip strength and tightrope performance. C57BL/6J mice were superior performers in tasks requiring balance and coordination, such as movement on stationary and rotating rods. In addition, the C57BL/6J strain generally exhibited greater locomotor activity, such as measured in open field and wheel-running tests. Significant age-related deficits were observed among A/J mice in tests of grip strength, balance rod, rotorod, and wheel activity; and among C57BL/6J mice, in balance rod, tightrope, exploratory activity, and wheel activity tests. Except for scores of exploratory activity (free versus forced exploration), the test measures tended to be uncorrelated; however, the degree and magnitude of intercorrelation among test scores increased with age. The results underscore the need to consider genotype in the assessment of age-related motor impairments in animal models.     

The rat exposure test: a model of mouse defensive behaviors

In order to facilitate behavioral, and potentially pharmacological, analyses of risk assessment behaviors in mice, a rat exposure test (RET) was devised and evaluated. This test provides a home chamber connected via a tunnel to a rat (predator) exposure area. Familiar substrate is provided to permit burying, and mouse subjects are habituated to the apparatus prior to exposure to an amphetamine-activated rat. In comparison to toy-rat-exposed controls, rat-exposed BALB/c mice showed significantly more risk assessment [stretch attend posture (SAP) and stretch approach], freezing, and avoidance (time in the home chamber), and less time in contact with the wire mesh screen between itself and the threat stimulus. When BALB/c, C57BL/6, CD-1, and Swiss-Webster mice were compared in this test, the two inbred strains (BALB/c and C57BL/6) tended to show more extreme values of particular defensive behaviors, compared to the two outbred strains (Swiss-Webster and CD-1). C57BL/6 mice showed more avoidance and higher levels of SAP, freezing, and burying than BALB/c and more than one or both outbred strains as well. BALB/c mice showed little defensive burying, both in comparison to toy-exposed controls (Experiment 1), and in comparison to the three other strains in Experiment 2. These findings are somewhat at variance with characterizations of anxiety in C57BL/6 and BALB/c mice, based on tests utilizing novel areas and noxious stimuli, suggesting strain differences in defensiveness to such stimuli, compared to antipredator defense levels. Nonetheless, with the exception of burying in BALB/c mice, all strains showed all defensive behaviors measured to the rat stimulus. In particular, SAP levels were substantial in all strains tested, suggesting the usefulness of this test in assessment of the role of risk assessment in defense.     

Olfactory bulbectomy in mice induces alterations in exploratory behavior

The olfactory bulbectomy syndrome is thought to represent a rodent model for psychomotor agitated depression. While this model has been extensively characterized in rats, fewer studies have been conducted with mice. Therefore, the present study aimed at extending the characterization of the OBX-induced behavioral syndrome in mice, using tests like open field, novel object exploration, novel cage and T-maze learning. OBX mice exhibited hyperactivity in a brightly illuminated open field, and also in a novel home cage as well as in the T-maze. Furthermore, OBX mice demonstrated increased exploratory behavior in the novel object test and in the T-maze. The complex alterations described here with respect to locomotion and exploration are robust and can be achieved by relatively simple test procedures. The extended behavioral characterization of the murine OBX model may contribute in particular to the increasing need to test transgenic mice for the presence of depression-like behaviors.     

Features of the Genetically Defined Anxiety in Mice

The behaviors of male mice of the C57BL/6J (C57), CBA/Lac (CBA) and BALB/c (BALB) strains have been studied in the plus-maze and open field tests for estimation of state anxiety in the stressful novel conditions, and in the cubic box test (exploration of novel cubic box) and the partition test (behavioral reactivity to the unfamiliar partner in the neighboring compartment) for estimation of trait anxiety in the unstressful familiar conditions of the home cage. Plus-maze data suggest that C57 mice are the more anxious than CBA and BALB ones. However, it was revealed the opposite rank order in the open field. The study on the effect of pre-testing in the one of test on the behavior in the other test revealed active behavioral strategy in C57 mice in any situations. The plus-maze behavior of CBA mice was affected to a much lesser extent than in C57 ones after pre-testing in the open field, but expressed changes were observed in open field behavior of CBA mice after pre-testing in the plus-maze. BALB mice displayed low-reactive behavior after any pre-testing exposure under the state anxiety-provoking conditions. Familiar environment revealed a higher level of trait anxiety in C57 than males of other two strains: CBA and BALB mice willingly explore unfamiliar partner and cubic box while C57 mice avoid its. Mainly genetically inherent state anxiety in CBA mice and trait anxiety in C57 mice has been suggested. Lowest state and trait indices of anxiety were revealed in BALB mice in these conditions.     

Differential genetic regulation of motor activity and anxiety-related behaviors in mice using an automated home cage task

Traditional behavioral tests, such as the open field test, measure an animal's responsiveness to a novel environment. However, it is generally difficult to assess whether the behavioral response obtained from these tests relates to the expression level of motor activity and/or to avoidance of anxiogenic areas. Here, an automated home cage environment for mice was designed to obtain independent measures of motor activity levels and of sheltered feeding preference during three consecutive days. Chronic treatment with the anxiolytic drug chlordiazepoxide (5 and 10 mg/kg/day) in C57BL/6J mice reduced sheltered feeding preference without altering motor activity levels. Furthermore, two distinct chromosome substitution strains, derived from C57BL/6J (host strain) and A/J (donor strain) inbred strains, expressed either increased sheltering preference in females (chromosome 15) or reduced motor activity levels in females and males (chromosome 1) when compared to C57BL/6J. Longitudinal behavioral monitoring revealed that these phenotypic differences maintained after adaptation to the home cage. Thus, by using new automated behavioral phenotyping approaches, behavior can be dissociated into distinct behavioral domains (e.g., anxiety-related and motor activity domains) with different underlying genetic origin and pharmacological responsiveness.     

Behavioral and biochemical changes monitored in two inbred strains of mice during exploration of an unfamiliar environment

Mice of the C57BL/6 (C57) and DBA/2 (DBA) strains were introduced individually in an unfamiliar environment (a large cage where food, water and sawdust had been removed). Over a 90-min period of observation, both strains presented a time-dependent decrease of locomotion and leaning and an increase of grooming. C57 mice were characterized by more cage cover climbing than DBA mice during the first 15-min stay in the new cage and by a significant decrease of this behavior after 90 min. During the first 60 min in the new environment, the DBA mice were less active than C57 mice, and both strains presented a significant increase of immobility after 90 min of test. After 30 min in the test situation, C57 presented a larger increase of plasma corticosterone levels than DBA mice. The plasma corticosterone levels were back to control values after 60 min of test in mice of the C57 strain and after 90 min in the DBA strain. Finally, both C57 and DBA mice presented a significant increase of homovanillic acid concentrations in the nucleus accumbens, but not in the striatum at 30, 60 and 90 min of testing. These results are discussed in terms of the possible involvement of mesolimbic dopaminergic system in mouse behavioral responses to an unfamiliar environment and of possible habituation to the stressful properties of this experience.     

Behavioral characterization of A/J and C57BL/6J mice using a multidimensional test: association between blood plasma and brain magnesium-ion concentration with anxiety

Up to 29% of all adults will experience an anxiety-related disorder during their lives. Treatment of these disorders is still difficult and the exact mechanisms and pathways behind anxiety disorders remain to be elucidated. Although evidence exists for genetically based susceptibility of human psychiatric diseases, risk genes have rarely been identified up to now. Inbred mouse strains are, together with the crosses and genetic reference populations derived from them, important tools for the genetic dissection of complex behavioral traits in the mouse. Thus, inbred mouse models of human anxiety may be a potent starting tool to search for candidate genes in mice, which could then via comparative genomics be translated to the human situation. In this paper we investigate whether the A/J and C57BL/6J mouse inbred strains differ in a limited number of motivational systems (anxiety, exploration, memory, locomotion, and social affinity), but especially in anxiety-related behavior from each other. Young adult individuals from both genders of A/J and C57BL/6J strains were behaviorally phenotyped using a multidimensional test: the modified hole board. This paradigm basically is a combination of the traditional hole board and the open field test allowing to test for anxiety-related avoidance behavior, risk assessment, arousal, exploration, memory, locomotor activity, and social affinity, using just one single test. An acute, aversive stimulus (intra-peritoneal injection with saline) was applied to the animals to test for the robustness of their behavioral phenotype. In addition, presumed physiological indicators for anxiety (circulating glucose, cholesterol, and corticosterone, adrenal tyrosine hydroxylase, and blood plasma and brain magnesium) were investigated. It could be concluded that C57BL/6J and A/J mice differ with respect to almost all tested motivational systems. For some measures, including anxiety-related behavioral parameters, there were clear gender effects. The high-anxiety phenotype of A/J mice could be shown to represent a primary and robust characteristic. Further, blood plasma and brain magnesium levels were significantly correlated with several anxiety-related behavioral parameters. These results emphasize the hypothesized, and possibly causal, association between magnesium status and emotionality.     

Behavioral responses of 129/Sv, C57BL/6J and DBA/2J mice to a non-predator aversive olfactory stimulus

We examined the behavior of three inbred mouse strains (129/SvPasIco, C57BL/6J, and DBA/2J) exposed to an object soaked with the chemical component of the aversive scent (toluquinone odor) emitted by a myriapod species (Ommatoiulus sabulosus) in the presence of a predator. Subjects were exposed to the odor for three consecutive days. Behavioral responses to the toluquinone odor were characterized both by an approach phase of risk assessment and by a repeated series of approach-avoid episodes. Results indicate that toluquinone exposure reduced completely, and in a strain independent fashion, selected behaviors such as crouching, catching and eating object. Other responses were strain-dependent: the DBA (DBA/2J) strain displayed defensive burying at high levels, C57 (C57BL/6J) mice performed high levels of withdrawal while the 129/Sv (129/SvPasIco) strain showed also high levels of stretch attend posture. Compared to other tasks, this test is ethological, simple, cheap and is not affected by strain differences in appetitive-sensory responses, as shown by some strain-independent responses. These features make this task as a good complement to any exploration-anxiety test battery.     

Differential effects of two types of environmental novelty on activity and sleep in BALB/cJ and C57BL/6J mice

Change in the sleeping environment can produce significant alterations in sleep. To determine how these alterations may vary with the amount of change and the relative reactivity of the sleeper, we examined the influences of environmental novelty on sleep in two mouse strains that differ in behavioral anxiety. Mice [BALB/cJ (n=7) and C57BL/6J (n=8)] were implanted for recording EEG and activity via telemetry. Following baseline data collection, activity and sleep were examined over 46 h after routine cage change, after placing a simple novel object (PVC Tee) in the home cage, and after handling controls. Mice of both strains showed immediate increases in activity and decreases in rapid eye movement sleep (REM) and non-REM (NREM) after cage change and novel object. Within strain, changes in activity and sleep were greater after cage change than after novel object. Changes in activity and sleep time were significantly correlated in each strain. Compared to C57BL/6J mice, BALB/cJ mice exhibited greater and longer duration initial reductions in sleep time, and greater increases in EEG slow wave activity power after cage change and novel object, but these changes were not followed with subsequent increases in sleep time. In contrast, C57BL/6J mice showed significantly greater subsequent increases in sleep time following the initial reductions induced by both manipulations. The results suggest that initial decreases and subsequent increases in sleep time are related to putative differences in the intensity of environmental novelty (cage change>novel object) and to previously described strain differences in anxiety (BALB/cJ>C57BL/6J).     

Habituation to the test cage influences amphetamine-induced locomotion and Fos expression and increases FosB/DeltaFosB-like immunoreactivity in mice

Pre-exposure to the testing cage (habituation or familiarization) is a common procedure aimed at reducing the interference of novelty-induced arousal and drug-independent individual differences on neural and behavioral measures. However, recent results suggest that this procedure might exert a major influence on the effects of addictive drugs. The present experiments tested the effects of repeated exposure to a test cage (1 h daily for four consecutive days) on amphetamine-induced locomotion and Fos expression as well as on FosB/DeltaFosB-like immunoreactivity in mice of the C57BL/6J and DBA/2J inbred strains that differ for the response to amphetamine, stress and novelty. Daily experiences with the test cage increased FosB/DeltaFosB-like immunoreactivity in the medial-prefrontal cortex of both strains of mice and in the caudate of mice of the C57 strain, as reported for repeated stress in the rat. Moreover, previous habituation to the test cage reduced the locomotor response to a low dose of amphetamine only in DBA mice while it reduced amphetamine-induced Fos expression in medial-prefrontal cortex, dorsal caudate and the accumbens shell of mice of the C57 strain. These results demonstrate indexes of stress-like plasticity in the brains of mice exposed to a procedure of familiarization to the testing environment. Moreover, they suggest that the procedure of daily familiarization influences the pattern of brain Fos expression induced by amphetamine. Finally, they indicate complex interactions between experience with the testing environment, genotype and drug.     

Behavioral Characterization of Wild Derived Male Mice (<Emphasis Type="Italic">Mus musculus musculus</Emphasis>) of the PWD/Ph Inbred Strain: High Exploration Compared to C57BL/6J

PWD/Ph is an inbred mouse strain derived from wild mice trapped in central Czech Republic. These mice are of the Mus musculus musculus subspecies, whose ancestors separated from those of Mus musculus domesticus about one million years ago. There is a high degree of variation in the genomic sequence and a wide range of phenotypes between PWD/Ph and standard laboratory inbred mouse strains, the genomes of which are principally Mus musculus domesticus in origin, making PWD/Ph mice an useful resource for complex trait research. As a first step in taking advantage of this resource, a preliminary characterization of the behavior of PWD/Ph mice was performed. Groups of 10 PWD/Ph and C57BL/6J male mice were tested in the open field, novel object exploration task and Morris water maze. PWD/Ph were marginally more anxious than C57BL/6J mice in the open field but subsequently displayed much higher levels of exploration and lower anxiety than C57BL/6J mice following introduction of a novel object. As C57BL/6J itself is rated as highly explorative among classical inbred strains, PWD/Ph probably represents an extreme among mouse strains for this specific behavior. PWD/Ph and C57BL/6J mice differed in their water escape training profiles in the Morris water maze, perhaps reflecting different motivational factors. However, there were no differences in overall cognitive ability (spatial learning) as both groups learned to find the hidden platform and performed equally well when the location of the platform was changed. This is the first quantification of the behavior of PWD/Ph mice and the results are promising for the potential of the consomic panel currently being generated with PWD/Ph and C57BL/6J as a tool for the molecular dissection of behavior.     

Nutrient preference and diet-induced adiposity in C57BL/6ByJ and 129P3/J mice

Purified carbohydrates and fats are usually palatable to humans and other animals, and their consumption often induces weight gain and accumulation of fat. In this study, we examined consumption of complex carbohydrates (cornstarch and Polycose) and fats (soybean oil and margarine) in mice from two inbred strains, C57BL/6ByJ and 129P3/J. At lower concentrations of liquid nutrients tested using two-bottle tests, when the amounts consumed had negligible energy content, the C57BL/6ByJ mice had higher acceptance of Polycose and soybean oil. This was probably due to strain differences in chemosensory perception of Polycose and oil. At higher concentrations, the mice consumed a substantial part of their daily energy from the macronutrient sources, however, there were no or only small strain differences in nutrient consumption. These small differences were probably due to strain variation in body size. The two strains also did not differ in chow intake. Despite similar energy intakes, access to the nutrients resulted in greater body weight (BW) gain in the C57BL/6ByJ mice than in the 129P3/J mice. The diet-induced weight gain was examined in detail in groups of 2-month-old C57BL/6ByJ and 129P3/J mice given ether chow, or chow and margarine to eat. Access to margarine did not increase total energy consumption of either strain. It increased BW and adiposity of the C57BL/6ByJ mice, but only after they reached the age of approximately 3 months. There were no differences in BW and adiposity between control and margarine-exposed 129P3/J mice. The results suggest that diet-induced adiposity in the B6 mice depends on age and does not depend on hyperphagia.