Social niche shapes social behavior and cortisol concentrations during adolescence in female guinea pigs.

Individualized social niches arise in social groups, resulting in divergent social behavior profiles among group members. During sensitive life phases, the individualized social niche can profoundly impact the development of social behavior and associated phenotypes such as hormone (e.g. cortisol) concentrations. Focusing on adolescence, we investigated the relationship between the individualized social niche, social behavior, and cortisol concentrations (baseline and responsiveness) in female guinea pigs. Females were pair-housed in early adolescence (initial social pair formation), and a social niche transition was induced after six weeks by replacing the partner with either a larger or smaller female. Regarding social behavior, dominance status was associated with aggression in both the initial social pairs and after the social niche transition, and the results suggest that aggression was rapidly and completely reshaped after the social niche transition. Meanwhile, submissive behavior was rapidly reshaped after the social niche transition, but this was incomplete. The dominance status attained in the initial social pair affected the extent of submissive behavior after the social niche transition, and this effect was still detected three weeks after the social niche transition. Regarding cortisol concentrations, higher baseline cortisol concentrations were measured in dominant females in the initial social pairs. After the social niche transition, cortisol responsiveness significantly increased for the females paired with a larger, older female relative to those paired with a smaller, younger female. These findings demonstrate that the social niche during adolescence plays a significant role in shaping behavior and hormone concentrations in females.

Structural enrichment for laboratory mice: exploring the effects of novelty and complexity.

Providing structural enrichment is a widespread refinement method for laboratory rodents and other animals in captivity. So far, animal welfare research has mostly focused on the effect of increased complexity either by accumulating or combining different enrichment items. However, increasing complexity is not the only possibility to refine housing conditions. Another refinement option is to increase novelty by regularly exchanging known enrichment items with new ones. In the present study, we used pair-housed non-breeding female C57BL/6J and DBA/2N mice to investigate the effect of novelty when applying structural enrichment. We used a double cage system, in which one cage served as home cage and the other as extra cage. While the home cage was furnished in the same way for all mice, in the extra cage we either provided only space with no additional enrichment items (space), a fixed set of enrichment items (complexity), or a changing set of enrichment items (novelty). Over 5 weeks, we assessed spontaneous behaviors, body weight, and extra cage usage as indicators of welfare and preference. Our main results showed that mice with access to structurally enriched extra cages (complexity and novelty) spent more time in their extra cages and complexity mice had lower latencies to enter their extra cages than mice with access to the extra cages without any structural enrichment (space). This indicates that the mice preferred the structurally enriched extra cages over the structurally non-enriched space cages. We found only one statistically significant difference between the novelty and complexity condition: during week 3, novelty mice spent more time in their extra cages than complexity mice. Although we did not detect any other significant differences between the novelty and complexity condition in the present study, more research is required to further explore the potential benefits of novelty beyond complexity.

Conditional on the social environment? Roots of repeatability in hormone concentrations of male guinea pigs.

Individual differences in behavioral and physiological traits among members of the same species are increasingly being recognized as important in animal research. On the group level, shaping of behavioral and hormonal phenotypes by environmental factors has been reported in different taxa. The extent to which the environment impacts behavior and hormones on the individual level, however, is rather unexplored. Hormonal phenotypes of guinea pigs can be shaped by the social environment on the group level: pair-housed and colony-housed males differ systematically in average testosterone and stressor-induced cortisol levels (i.e. cortisol responsiveness). The aim of the present study was to evaluate whether repeatability and individual variance components (i.e. between- and within-individual variation) of hormonal phenotypes also differ in different social environments. To test this, we determined baseline testosterone, baseline cortisol, and cortisol responsiveness after challenge in same-aged pair-housed and colony-housed guinea pig males over a period of four months. We found comparable repeatability for baseline cortisol and cortisol responsiveness in males from both social conditions. In contrast, baseline testosterone was repeatable only in males from colonies. Interestingly, this result was brought about by significantly larger between-individual variation of testosterone, that was not explained by differences in dominance rank. Individualized social niches differentiated under complex colony, but not pair housing, could be an explanation for this finding.

The power of a touch: Regular touchscreen training but not its termination affects hormones and behavior in mice.

Touchscreen-based procedures are increasingly used in experimental animal research. They not only represent a promising approach for translational research, but have also been highlighted as a powerful tool to reduce potential experimenter effects in animal studies. However, to prepare the animals for a touchscreen-based test, an often time-consuming training phase is required that has itself been shown to cause increased adrenocortical activity and anxiety-like behavior in mice. While these findings point at a potentially negative effect of touchscreen training at first glance, results have also been discussed in light of an enriching effect of touchscreen training. The aim of the present study was therefore to shed more light on recently reported touchscreen training effects, with a particular focus on the termination of the training routine. Specifically, we investigated whether the termination of regular touchscreen training could constitute a loss of enrichment for mice. Thus, we assessed fecal corticosterone metabolites (FCMs), exploratory-, anxiety-like and home cage behavior in touchscreen-trained mice in comparison to food restricted and ad libitum fed mice, as a restricted diet is an integral part of the training process. Furthermore, we compared these parameters between mice that were continuously trained and mice whose training was terminated 2 weeks earlier. Our results confirm previous findings showing that a mild food restriction increases the animals' exploratory behavior and shifts their activity rhythm. Moreover, touchscreen training was found to increase FCM levels and anxiety-like behavior of the mice. However, no effect of the termination of touchscreen training could be detected, a finding which contradicts the enrichment loss hypothesis. Therefore, we discuss two alternative explanations for the findings. Yet, the current state of knowledge is not sufficient to draw final conclusions at this stage. In compliance with the refinement endeavors for laboratory animals, further research should assess the severity of touchscreen procedures to ensure a responsible and well-founded use of animals for experimental purposes.

Correction: Do multiple experimenters improve the reproducibility of animal studies?

[This corrects the article DOI: 10.1371/journal.pbio.3001564.].

Transcriptional profiles in the mouse amygdala after a cognitive judgment bias test largely depend on the genotype.

Background: The amygdala is crucial for emotional cognitive processing. Affective or emotional states can bias cognitive processes, including attention, memory, and decision-making. This can result in optimistic or pessimistic behaviors that are partially driven by the activation of the amygdala. The resulting emotional cognitive bias is a common feature of anxiety and mood disorders, both of which are interactively influenced by genetic and environmental factors. It is also known that emotional cognitive biases can be influenced by environmental factors. However, little is known about the effects of genetics and/or gene-environment interactions on emotional cognitive biases. We investigated the effects of the genetic background and environmental enrichment on the transcriptional profiles of the mouse amygdala following a well-established cognitive bias test. Methods: Twenty-four female C57BL/6J and B6D2F1N mice were housed either in standard (control) conditions or in an enriched environment. After appropriate training, the cognitive bias test was performed on 19 mice that satisfactorily completed the training scheme to assess their responses to ambiguous cues. This allowed us to calculate an "optimism score" for each mouse. Subsequently, we dissected the anterior and posterior portions of the amygdala to perform RNA-sequencing for differential expression and other statistical analyses. Results: In general, we found only minor changes in the amygdala's transcriptome associated with the levels of optimism in our mice. In contrast, we observed wide molecular effects of the genetic background in both housing environments. The C57BL/6J animals showed more transcriptional changes in response to enriched environments than the B6D2F1N mice. We also generally found more dysregulated genes in the posterior than in the anterior portion of the amygdala. Gene set overrepresentation analyses consistently implicated cellular metabolic responses and immune processes in the differences observed between mouse strains, while processes favoring neurogenesis and neurotransmission were implicated in the responses to environmental enrichment. In a correlation analysis, lipid metabolism in the anterior amygdala was suggested to influence the levels of optimism. Conclusions: Our observations underscore the importance of selecting appropriate animal models when performing molecular studies of affective conditions or emotional states, and suggest an important role of immune and stress responses in the genetic component of emotion regulation.

Once an optimist, always an optimist? Studying cognitive judgment bias in mice.

Individuals differ in the way they judge ambiguous information: some individuals interpret ambiguous information in a more optimistic, and others in a more pessimistic way. Over the past two decades, such "optimistic" and "pessimistic" cognitive judgment biases (CJBs) have been utilized in animal welfare science as indicators of animals' emotional states. However, empirical studies on their ecological and evolutionary relevance are still lacking. We, therefore, aimed at transferring the concept of "optimism" and "pessimism" to behavioral ecology and investigated the role of genetic and environmental factors in modulating CJB in mice. In addition, we assessed the temporal stability of individual differences in CJB. We show that the chosen genotypes (C57BL/6J and B6D2F1N) and environments ("scarce" and "complex") did not have a statistically significant influence on the responses in the CJB test. By contrast, they influenced anxiety-like behavior with C57BL/6J mice and mice from the "complex" environment displaying less anxiety-like behavior than B6D2F1N mice and mice from the "scarce" environment. As the selected genotypes and environments did not explain the existing differences in CJB, future studies might investigate the impact of other genotypes and environmental conditions on CJB, and additionally, elucidate the role of other potential causes like endocrine profiles and epigenetic modifications. Furthermore, we show that individual differences in CJB were repeatable over a period of seven weeks, suggesting that CJB represents a temporally stable trait in laboratory mice. Therefore, we encourage the further study of CJB within an animal personality framework.

The Impact of Varying Food Availability on Gene Expression in the Liver: Testing the Match-Mismatch Hypothesis.

Background: During early phases of life, such as prenatal or early postnatal development and adolescence, an organism's phenotype can be shaped by the environmental conditions it experiences. According to the Match-Mismatch hypothesis (MMH), changes to this environment during later life stages can result in a mismatch between the individual's adaptations and the prevailing environmental conditions. Thus, negative consequences in welfare and health can occur. We aimed to test the MMH in the context of food availability, assuming adolescence as a sensitive period of adaptation. Methods: We have previously reported a study of the physiological and behavioral effects of match and mismatch conditions of high (ad libitum) and low (90% of ad libitum intake) food availability from adolescence to early adulthood in female C57BL/6J mice (n = 62). Here, we performed RNA-sequencing of the livers of a subset of these animals (n = 16) to test the effects of match and mismatch feeding conditions on the liver transcriptome. Results: In general, we found no effect of the match-mismatch situations. Contrarily, the amount of food available during early adulthood (low vs. high) drove the differences we observed in final body weight and gene expression in the liver, regardless of the amount of food available to the animals during adolescence. Many of the differentially expressed genes and the corresponding biological processes found to be overrepresented overlapped, implicating common changes in various domains. These included metabolism, homeostasis, cellular responses to diverse stimuli, transport of bile acids and other molecules, cell differentiation, major urinary proteins, and immunity and inflammation. Conclusions: Our previous and present observations found no support for the MMH in the context of low vs high food availability from adolescence to early adulthood in female C57BL/6J mice. However, even small differences of approximately 10% in food availability during early adulthood resulted in physiological and molecular changes with potential beneficial implications for metabolic diseases.

Do multiple experimenters improve the reproducibility of animal studies?

The credibility of scientific research has been seriously questioned by the widely claimed "reproducibility crisis". In light of this crisis, there is a growing awareness that the rigorous standardisation of experimental conditions may contribute to poor reproducibility of animal studies. Instead, systematic heterogenisation has been proposed as a tool to enhance reproducibility, but a real-life test across multiple independent laboratories is still pending. The aim of this study was therefore to test whether heterogenisation of experimental conditions by using multiple experimenters improves the reproducibility of research findings compared to standardised conditions with only one experimenter. To this end, we replicated the same animal experiment in 3 independent laboratories, each employing both a heterogenised and a standardised design. Whereas in the standardised design, all animals were tested by a single experimenter; in the heterogenised design, 3 different experimenters were involved in testing the animals. In contrast to our expectation, the inclusion of multiple experimenters in the heterogenised design did not improve the reproducibility of the results across the 3 laboratories. Interestingly, however, a variance component analysis indicated that the variation introduced by the different experimenters was not as high as the variation introduced by the laboratories, probably explaining why this heterogenisation strategy did not bring the anticipated success. Even more interestingly, for the majority of outcome measures, the remaining residual variation was identified as an important source of variance accounting for 41% (CI95 [34%, 49%]) to 72% (CI95 [58%, 88%]) of the observed total variance. Despite some uncertainty surrounding the estimated numbers, these findings argue for systematically including biological variation rather than eliminating it in animal studies and call for future research on effective improvement strategies.

When left is right: The effects of paw preference training on behaviour in mice.

Spontaneous limb preferences exist in numerous species. To investigate the underlying mechanisms of these preferences, different methods, such as training, have been developed to shift preferences artificially. However, studies that systematically examine the effects of shifting preferences on behaviour and physiology are largely missing. Therefore, the aim of this study was to assess the impact of shifting paw preferences via training on spontaneous home cage behaviour, as well as anxiety-like behaviour and exploratory locomotion (Elevated plus maze test, Dark light test, Open field test, Free exploration test), learning performance (Labyrinth-maze) and stress hormones (fecal corticosterone metabolites) in laboratory mice (Mus musculus f. domestica). For this, we assessed spontaneous paw preferences of C57BL/6J females (Nambilateral = 23, Nleft = 23, Nright = 25). Subsequently, half of the individuals from each category were trained once a week for four weeks in a food-reaching task to use either their left or right paw, respectively, resulting in six groups: AL, AR, LL, LR, RL, RR. After training, a battery of behavioural tests was performed and spontaneous preferences were assessed again. Our results indicate that most mice were successfully trained and the effect of training was present days after training. However, a significant difference of preferences between RL and LL mice during training suggests a rather low training success of RL mice. Additionally, preferences of L mice differed from those of A and R mice after training, indicating differential long-term effects of training in these groups. Furthermore, left paw training led to higher levels of self-grooming, possibly as a displacement behaviour, and more time spent in the light compartment of the Dark light test. However, overall, there was no systematic influence of training on behavioural measures and stress hormones. Different explanations for this lack of influence, such as the link between training and hemispheric functioning or the intensity and ecological relevance of the training, are discussed.

Repeatability of endocrine traits and dominance rank in female guinea pigs.

BACKGROUND: Glucocorticoids (e.g. cortisol) are associated with variation in social behavior, and previous studies have linked baseline as well as challenge-induced glucocorticoid concentrations to dominance status. It is known that cortisol response to an acute challenge is repeatable and correlates to social behavior in males of many mammal species. However, it is unclear whether these patterns are also consistent for females. The aim of this study was to investigate whether baseline and response cortisol concentrations are repeatable in female guinea pigs (Cavia aperea f. porcellus) and whether dominance rank is stable and correlated to baseline cortisol concentration and/or cortisol responsiveness. RESULTS: Our results show that cortisol responsiveness (after 1 h: R = 0.635, 95% CI = 0.229, 0.927; after 2 h: R = 0.764, 95% CI = 0.433, 0.951) and dominance rank (R = 0.709, 95% CI = 0.316, 0.935) of females were significantly repeatable after six weeks but not correlated. Baseline cortisol was not repeatable (R = 0, 95% CI = 0, 0.690) and also did not correlate to dominance rank. Furthermore, the difference in repeatability estimates of baseline and response values was due to high within-individual variance of baseline cortisol concentration; the amount of between-individual variance was similar for baseline cortisol and the two measures of cortisol responsiveness. CONCLUSIONS: Females occupying different dominance ranks did not have long-term differences in cortisol concentrations, and cortisol responsiveness does not seem to be significantly involved in the maintenance of dominance rank. Overall, this study reveals the remarkable stability of cortisol responsiveness and dominance rank in a female rodent, and it remains an open question whether the magnitude of cortisol responsiveness is adaptive in social contexts for females.

Effects of castration and sterilization on baseline and response levels of cortisol-A case study in male guinea pigs.

An uncontrolled reproduction of animals in human hands should be avoided. To meet this goal, animals are widely castrated, i.e., the gonads are completely removed. Since the gonads are the most important source of sex hormones, this is a serious intervention in the entire endocrine system of an organism. Sterilization is a much less invasive procedure. Thus, it could have advantages over castration. Therefore, the overall aim of this study was to analyze the effect of castration vs. sterilization on the release of glucocorticoids, i.e., an important indicator for welfare. Taking domestic guinea pigs as a model system, we studied baseline and response cortisol values (cortisol is the main glucocorticoid in guinea pigs) in castrated, sterilized, sham-operated and intact males and baseline values in their cohoused females. Whereas baseline values of males did not differ between the groups, castrated males showed significantly higher cortisol response levels than intact, sham-operated and sterilized males. Females housed with castrated, sterilized, sham-operated or intact males did not differ in their cortisol concentrations, neither shortly after being placed with the respective male or after being co-housed for several weeks. Overall, the results support the hypothesis that castrated males exhibited a higher cortisol responsiveness during acute challenge which could point to a generalized impaired welfare of castrated males in comparison to intact, sham-operated and sterilized males. Our results provide first evidence for a potential negative impact of castration on the animals' welfare, while at the same time pointing toward sterilization representing a less invasive, promising alternative. Therefore, the results may stimulate future research on this topic to further detect potential welfare-related side effects of castration.

Behavioral lateralization of mice varying in serotonin transporter genotype.

In humans, non-right-handedness is associated with a higher incidence of psychiatric disorders. Since serotonin seems to be involved in both, the development of psychiatric disorders and lateralization, the present study focuses on the effect of the serotonin transporter (5-HTT) gene on behavioral lateralization. For this, we used the 5-HTT knockout mouse model, a well-established animal model for the study of human depression and anxiety disorders. For female mice from all three 5-HTT genotypes (wild type, heterozygous, and homozygous knockout), we repeatedly observed the direction and strength of lateralization of the following four behaviors: grid climbing (GC), food-reaching in an artificial test situation (FRT), self-grooming (SG), and barrier crossing (BC), with the FRT being the standard test for assessing behavioral lateralization in mice. We found no association between behavioral lateralization and 5-HTT genotype. However, in accordance with previous findings, the strength and temporal consistency of lateralization differed between the four behaviors observed. In conclusion, since the 5-HTT genotype did not affect behavioral lateralization in mice, more research on other factors connected with behavioral lateralization and the development of symptoms of psychiatric disorders, such as environmental influences, is needed.

Individuality meets plasticity: Endocrine phenotypes across male dominance rank acquisition in guinea pigs living in a complex social environment.

The time of dominance rank acquisition is a crucial phase in male life history that often affects reproductive success and hence fitness. Hormones such as testosterone and glucocorticoids can influence as well as be affected by this process. At the same time, hormone concentrations can show large individual variation. The extent to which such variation is repeatable, particularly in dynamic social settings, is a question of current interest. The aim of the present study was therefore to investigate how dominance rank and individual differences contribute to variance in hormone concentrations during male rank acquisition in a complex social environment. For this purpose, dominance rank as well as baseline testosterone, baseline cortisol, and cortisol responsiveness after exposure to a novel environment were determined in colony-housed guinea pig males from late adolescence through adulthood. Hormone-dominance relationships and repeatability of hormone measures beyond their relation to rank were assessed. There was a significant positive relationship between baseline testosterone and rank, but this link became weaker with increasing age. Baseline cortisol or cortisol responsiveness, in contrast, were not significantly related to dominance. Notably, all three endocrine parameters were significantly repeatable independent of dominance rank from late adolescence through adulthood. Baseline testosterone and cortisol responsiveness showed a significantly higher repeatability than baseline cortisol. This suggests that testosterone titres and cortisol responsiveness represent stable individual attributes even under complex social conditions.

Regular touchscreen training affects faecal corticosterone metabolites and anxiety-like behaviour in mice.

Automated touchscreen techniques find increasing application for the assessment of cognitive function in rodents. However, hardly anything is known about the potential impact of touchscreen-based training and testing procedures on the animals under investigation. Addressing this question appears particularly important in light of the long and intensive training phases required for most of the operant tasks. Against this background, we here investigated the influence of regular touchscreen training on hormones and behaviour of mice. Faecal corticosterone metabolites (FCMs), reflecting corticosterone levels around the time of treatment, were significantly increased in touchscreen-trained mice, even one week after the training phase was already terminated. Such an effect was not detected on baseline FCMs. Thus, regular touchscreen training can be assumed to cause long-term effects on hypothalamus-pituitary-adrenal axis activity. Furthermore, anxiety-like behaviour was increased in touchscreen-trained mice two weeks after the end of the training phase. Traditionally, this would be interpreted as a negative influence of the training procedure on the animals' affective state. Yet, we also provide two alternative explanations, taking the possibility into account that touchscreen training might have enriching properties.

The impact of varying food availability on health and welfare in mice: Testing the Match-Mismatch hypothesis.

During early phases of life, an organism's phenotype can be shaped by the environmental conditions which it experiences. If the conditions change subsequently, the mismatch between the environment in early and later life could have negative effects on the individual's health and welfare. The aim of this study was to systematically test the predictions of this Match-Mismatch hypothesis in laboratory mice. Therefore, female C57BL/6 J mice were exposed to matching or mismatching combinations of low and high food availability in adolescence and early adulthood. A comprehensive analysis of various physiological and behavioral parameters was conducted. No indication of a mismatch effect was found, which might be attributed to the specific ecology of mice. Alternatively, food availability might cause a shaping of the phenotype only during the prenatal or early postnatal development. However, various effects of low vs high food availability were found regarding the individuals' physiology and, to a small extent, their behavior. Low food availability caused higher concentrations of fecal corticosterone metabolites, as well as higher liver and lower spleen weights, suggesting an adaptation of the metabolism to this situation.

Not all mice are alike: Mixed-strain housing alters social behaviour.

The use of millions of mice in scientific studies worldwide emphasises the continuing need for a reduction of sample sizes, however, not at the expense of scientific validity. Split-plot designs have been suggested to enhance statistical power while allowing a reduction of animal numbers in comparison to traditional experimental designs. Recently, a promising approach of a split-plot design has been implemented and proven useful using mixed-strain housing of at least three different mouse strains. However, the impact of co-housing different strains of mice in one cage on animal welfare has still to be defined. This study aimed at comparing the effects of mixed-strain and same-strain housing of female C57BL/6J and DBA/2N mice on welfare and behaviour in two experimental phases. In a first phase, mice were housed in either mixed- or same-strain pairs. Home cage behaviour, activity rhythm, body weight, and faecal corticosterone metabolites were assessed. Furthermore, tests for anxiety-like and exploratory behaviour as well as spatial learning were performed. In a second phase, sociability was investigated in newly formed mixed-strain quartets. Mixed-strain housing did not induce alterations in anxiety, locomotion, learning, stereotypic behaviour, and stress hormone levels. However, changes in social behaviours and activity rhythm were observed. Increased agonistic and decreased socio-positive behaviours might point towards mild impacts on welfare in C57BL/6J mice under co-housing conditions. Altogether, scientific research may greatly benefit from co-housing mice of different strains within the same cages (e.g. for the realisation of a split-plot design), provided that strains are carefully selected for compatibility.

Improving reproducibility in animal research by splitting the study population into several 'mini-experiments'.

In light of the hotly discussed 'reproducibility crisis', a rethinking of current methodologies appears essential. Implementing multi-laboratory designs has been shown to enhance the external validity and hence the reproducibility of findings from animal research. We here aimed at proposing a new experimental strategy that transfers this logic into a single-laboratory setting. We systematically introduced heterogeneity into our study population by splitting an experiment into several 'mini-experiments' spread over different time points a few weeks apart. We hypothesised to observe improved reproducibility in such a 'mini-experiment' design in comparison to a conventionally standardised design, according to which all animals are tested at one specific point in time. By comparing both designs across independent replicates, we could indeed show that the use of such a 'mini-experiment' design improved the reproducibility and accurate detection of exemplary treatment effects (behavioural and physiological differences between four mouse strains) in about half of all investigated strain comparisons. Thus, we successfully implemented and empirically validated an easy-to-handle strategy to tackle poor reproducibility in single-laboratory studies. Since other experiments within different life science disciplines share the main characteristics with the investigation reported here, these studies are likely to also benefit from this approach.

Effects of different social experiences on emotional state in mice.

A comprehensive understanding of animals' emotions can be achieved by combining cognitive, behavioural, and physiological measures. Applying such a multi-method approach, we here examined the emotional state of mice after they had made one of three different social experiences: either a mildly "adverse", a "beneficial", or a "neutral" experience. Using a recently established touchscreen paradigm, cognitive judgement bias was assessed twice, once before and once after the respective experience. Anxiety-like behaviour was examined using a standardised battery of behavioural tests and faecal corticosterone metabolite concentrations were measured. Surprisingly, only minor effects of the social experiences on the animals' cognitive judgement bias and no effects on anxiety-like behaviour and corticosterone metabolite levels were found. It might be speculated that the experiences provided were not strong enough to exert the expected impact on the animals' emotional state. Alternatively, the intensive training procedure necessary for cognitive judgement bias testing might have had a cognitive enrichment effect, potentially countering external influences. While further investigations are required to ascertain the specific causes underlying our findings, the present study adds essential empirical data to the so far scarce amount of studies combining cognitive, behavioural, and physiological measures of emotional state in mice.

Adaptive reshaping of the hormonal phenotype after social niche transition in adulthood.

Phenotypic plasticity allows individuals to adjust traits to the environment. Whether long-term adjustments of the phenotype occur during later life stages is largely unknown. To address this question, we examined whether hormonal phenotypes that are shaped by the environment during adolescence can still be reshaped in full adulthood. For this, guinea pig males were either housed in mixed-sex colonies or in heterosexual pairs. In adulthood, males were individually transferred to pair housing with a female. This way, a social niche transition was induced in colony-housed males, but not in pair-housed males. Before transfer, corresponding to findings in adolescence, adult colony-housed males showed significantly higher baseline testosterone levels and lower cortisol responsiveness than pair-housed males. One month after transfer, the hormonal phenotype of colony-housed males was changed towards that of pair-housed males: animals showed comparable baseline testosterone levels and cortisol responsiveness was significantly increased in colony-housed males. This endocrine readjustment builds the basis for an adaptive behavioural tactic in the new social situation. Thus, an adaptive change of the behavioural phenotype may still occur in adulthood via modification of underlying mechanisms. This suggests a greater role for developmental plasticity in later life stages than is commonly presumed.