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Precursors to human theory of mind and action understanding abilities of dogs (Canis familiaris)
PhD Arbeit - Veterinärmedizinische Universität Wien - 2024
Aus rechtlichen Gründen sind nicht alle Teile dieser Arbeit frei zugänglich. Der Zugriff auf den elektronischen Volltext ist auf Angehörige der Veterinärmedizinischen Universität Wien beschränkt. Bitte einloggen!PhD thesis - University of Veterinary Medicine Vienna - 2024
The full text is only available to university members. Please log in!The work presented in this thesis investigated pet dogs’ possible precursors to the human theory of mind and action understanding abilities. The comparative study of these topics can help shed light on the nature and origin of such abilities in humans. It has been suggested that, through a process of convergent evolution, dogs might have evolved socio-cognitive abilities functionally comparable to those of human children. My behavioural experiments, using a non-verbal change of location task, highlighted that dogs are sensitive to very subtle human behavioural cues connected to “knowing”. Indeed, in the context of a search game, they reacted differently to the misleading suggestion coming from an experimenter who knew the correct location of food compared to the misleading suggestion from an experimenter who was mistaken about the location of food. Unexpectedly, more dogs followed the misleading suggestion coming from the mistaken experimenter. However subtle the manipulation that dogs reacted to, this non-verbal task still involved a behavioural difference (whether the experimenter was present or absent in the room during the crucial displacement of food) between conditions, hence it cannot provide strong evidence of false belief understanding. Additionally, several controls are still missing in the canine literature, to rule out the multiple alternative explanations that have been proposed to explain the scarce positive findings of non-verbal, implicit false-belief tasks with infants and apes. For these reasons, while not excluding it, my study also does not strongly support the hypothesis that dogs might represent and attribute mental states to others in a way comparable to what human children do from about 4 years of age on. Instead, dogs’ behaviour in my study was consistent with that of younger infants and chimpanzees tested on “altercentric bias” tasks. Hence, it seems that dogs can at least be influenced by human mental states implicitly. With my eye-tracking experiments, I elucidated how dogs visually attend to object-directed actions performed by others, a foundational component of many ToM abilities. In a first study, I presented a conspecific and a human agent approaching and acting on a toy. I also varied whether the human agent moved normally or performed movements closer to dogs’ own motor possibilities. Examples of the first case are bipedal walking and kicking with a foot or grasping with fingers; examples of the second case are crawling and pushing away using an upper limb or grasping with mouth. Unlike primates (including humans) tested in previous studies, dogs did not predict others’ action targets by directly matching the observed movements on their own motor repertoire, but rather relied on visual cues that they probably learned to associate to salient action effects during their ontogeny. Their gaze arrival times to the target object seemed mainly driven by the saliency of the agent performing the action and were only rarely predictive (i.e., arriving to the object before the agent made contact with it). In a second study, I adapted for dogs Woodward’s paradigm. The results suggested that, unlike apes and humans infants, dogs might preferentially encode the spatial location where agents act rather the identity of the object they act upon. Finally, across my studies, dogs’ looking patterns showed sensitivity to the species and animacy of the agents shown in videos on a computer screen, with longer looking times to a conspecific than to a human agent and to a human agent than to an inanimate, though selfpropelled, object. Overall, these findings highlighted only a few similarities between dog and human behaviour, for example the tendency to “trust” misleading communication. Mostly, however, I found the processing of social stimuli diverged between the two species. Because these findings might be due to methodological challenges and to (not yet clarified) differences between dogs’ and primates’ processing of social stimuli, it might be premature to conclude that, at least in the perspective-taking and action understanding domains, evolution did not shape dogs’ cognition similarly to that of humans. From mine and previous findings, however, it is clear that dogs’ social cognition is extremely well attuned to reading human behaviour and more research is needed to test the convergent evolution hypothesis in the social domain
Comparison of usage of indocyanine green, 5-aminolevulinic acid, methylene blue and fluorescein sodium in oncology in human and veterinary medicine
Diplomarbeit - Veterinärmedizinische Universität Wien - 2024Diese Diplomarbeit untersucht die Anwendung von fluoreszierenden Farbstoffen – Indocyaningrün, 5-Aminolevulinsäure, Methylenblau und Fluoreszein-Natrium – in der Onkologie der Veterinärmedizin der letzten zehn Jahre und vergleicht die Ergebnisse mit dem aktuellen Stand der Humanmedizin. Die Farbstoffe ermöglichen eine verbesserte Darstellung von Tumorgewebe, was die Erkennung von Tumoren, Tumorrändern, Metastasen und Lymphknoten während chirurgischer Eingriffe erleichtert. Der Fokus der Arbeit liegt auf der Nutzung dieser Farbstoffe bei Hunden und Katzen und vergleicht die erlangten Ergebnisse mit aktuellen Studien der Humanmedizin. Eine systematische Literaturrecherche von 2014 bis 2024 zeigt, dass diese Farbstoffe in der Humanmedizin bereits umfassend verwendet werden, während ihr Einsatz in der Veterinärmedizin bisher nur begrenzt untersucht wurde. Indocyaningrün und Methylenblau zeigen in der Veterinärmedizin großes Potential, etwa bei der Färbung von Lymphknoten und der Abgrenzung von Tumorrändern, jedoch kommt es besonders bei der Verwendung von Indocyaningrün häufig zu falsch positiven Ergebnissen. 5-Aminolevulinsäure ist durch seine höhere Tumorspezifität vielversprechend, die bisherigen Studien umfassen jedoch nur sehr kleine Stichproben. Die aktuelle Forschungslage zu Fluoreszin-Natrium in der veterinärmedizinischen Onkologie ist stark begrenzt. Die Anzahl an Berichten von unerwünschten Nebenwirkungen im Zusammenhang mit der Verwendung der Farbstoffe bei Hund und Katze ist gering. Die Arbeit identifiziert Herausforderungen wie falsch-positive Ergebnisse aufgrund von Entzündungen und sehr kleine Versuchsgruppen, und zeigt den dringenden Bedarf an weiteren Studien, um die Techniken für den Einsatz in der Veterinärmedizin zu optimieren. Insgesamt zeigen die Ergebnisse, dass der Einsatz von Fluorophoren die chirurgischen Ergebnisse in der Onkologie der Tiermedizin verbessern und die Rezidivraten von Tumoren verringern kann. Weitere Forschung ist jedoch notwendig, um die klinische Anwendbarkeit und Sicherheit dieser Methoden bei Tieren weiter zu validieren.Diploma thesis - University of Veterinary Medicine Vienna - 2024This diploma thesis investigates the use of four fluorescent dyes—indocyanine green, 5- aminolevulinic acid, methylene blue, and fluorescein sodium — in oncology veterinary medicine and compares the findings with current state in human medicine. Fluorescent dyes play a crucial role in enhancing the visualization of neoplastic tissues, aiding in the precise detection of tumors, tumor margins, metastases and lymph nodes during surgical procedures. This thesis focuses on the application of the fluorophores in dogs and cats, comparing the findings with recent studies from human medicine. A systematic review of literature from 2014 to 2024 revealed that while all four dyes are already utilized in human oncology, their application in veterinary medicine remains underexplored. Indocyanine green and methylene blue show the most promise for sentinel lymph node mapping and tumor margin delineation, nevertheless, false positive results are commonly observed with the use of indocyanine green. 5-aminolevulinic acid is notable for its greater tumor specificity, however, the existing studies are limited by small sample sizes. The current research situation on fluorescein sodium in veterinary oncology is very limited as well. The number of reported adverse effects associated with the fluorophores in dogs and cats was low. The study identifies challenges such as false-positive results due to inflammation and very small sample sizes, highlighting the urgent need for further research to optimize these techniques for the clinical use in veterinary medicine. Overall, the findings suggest that the use of fluorophores can improve surgical outcomes in veterinary oncology and reduce tumor recurrence rates. However, additional research is needed to further validate the clinical applicability and safety of these methods in dogs and cats
Vorkommen und gesundheitliche Auswirkungen von Mykotoxinen im Pferdeheu
Diploma thesis - University of Veterinary Medicine Vienna - 2024Hay is the most important roughage for horses, and its quality is crucial for their health (1, 2). However, mold and their toxic metabolites, mycotoxins, are frequently detected in horse hay (3–10). As the occurrence of mycotoxins in horse hay and the associated health risks for horses have been only limitedly researched (4, 11), this study aims to summarize the current scientific knowledge in a comprehensive literature review. The digestive system of horses places specific demands on hay quality (1, 2, 12), making regular assessment of hay quality in practice essential (1, 2, 13). Mycotoxins are chemically heterogeneous and highly toxic substances produced by specific molds both in the field and during storage (14– 16). In addition to horse hay, they have also been detected in individual and mixed feed, straw, and pasture grasses (4, 17–19). The most frequently identified mycotoxins include deoxynivalenol, zearalenone, fumonisin B1, aflatoxin B1, and ochratoxin A in hay and concentrates; medically relevant, however, are ergovaline, lolitrem B, and slaframine, which are predominantly detected in fresh forage. Mycotoxins can cause a wide range of symptoms in horses, affecting the gastrointestinal, respiratory, and reproductive tracts, as well as the immune and nervous systems (11, 20, 21). As only a few toxins can be definitively linked to specific diseases, diagnosis and treatment often prove challenging (20). Understanding the growth conditions of molds and the most common sources of contamination during hay production is crucial for implementing effective preventive measures to reduce mycotoxin exposure (11, 13). Given that the potential risk to horses is considered high according to current literature, prevention plays a central role. Due to the inconsistent study findings, there is significant research need to derive concrete, practical recommendations.Diplomarbeit - Veterinärmedizinische Universität Wien - 2024Heu ist das bedeutendste Grundfuttermittel für Pferde und seine Qualität entscheidend für ihre Gesunderhaltung (1, 2). Im Pferdeheu werden jedoch wiederkehrend Schimmelpilze und ihre toxischen Stoffwechselprodukte, die Mykotoxine, nachgewiesen (3–10). Da das Mykotoxin-Vorkommen im Pferdeheu und das davon ausgehende Gesundheitsrisiko für Pferde bisher nur begrenzt erforscht sind (4, 11), zielt diese Arbeit darauf ab, den aktuellen wissenschaftlichen Kenntnisstand durch eine umfassende Literaturrecherche zusammenzufassen.
Das Verdauungssystem der Pferde stellt besondere Anforderungen an die Qualität des Heus (1, 2, 12), was eine regelmäßige Überprüfung der Heuqualität in der Praxis essenziell macht (1, 2, 13). Mykotoxine sind chemisch heterogene und hochtoxische Substanzen, die sowohl auf dem Feld als auch während der Lagerung durch spezifische Schimmelpilze gebildet werden (14–16). Neben dem Pferdeheu wurden sie auch in Einzel- und Mischfuttermitteln, Stroh und Weidegrünland nachgewiesen (4, 17–19). Zu den besonders häufig identifizierten Mykotoxinen zählen Deoxynivalenol, Zearalenon, Fumonisin B1, Aflatoxin B1 und Ochratoxin A in Heu und Kraftfuttermitteln; medizinisch relevant sind jedoch auch Ergovalin, Lolitrem B und Slaframin, die vorwiegend in Grünfutter nachgewiesen werden.
Mykotoxine können beim Pferd unterschiedlichste Symptome hervorrufen, die den Gastrointestinal-, Respirations-, und Reproduktionstrakt sowie das Immun- und Nervensystem betreffen (11, 20, 21). Da nur wenige Toxine eindeutig mit spezifischen Krankheitsbildern in Verbindung gebracht werden können, erweisen sich Diagnose und Behandlung oft als schwierig (20).
Kenntnisse über die Wachstumsbedingungen von Schimmelpilzen und die häufigsten Kontaminationsquellen bei der Heuherstellung sind wichtig, um wirksame Präventionsmaßnahmen zur Reduktion der Mykotoxinbelastung umzusetzen (11, 13).
Da das Gefährdungspotenzial für Pferde nach aktueller Fachliteratur als hoch eingeschätzt wird, kommt der Prävention eine zentrale Rolle zu. Aufgrund der uneinheitlichen Studienlage besteht erheblicher Forschungsbedarf, um konkrete, praxisnahe Empfehlungen ableiten zu können
A lineage-specific STAT5BN642H mouse model to study NK-cell leukemia
Patients with T- and natural killer (NK)-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent STAT5B mutation is STAT5BN642H, which is known to drive murine T-cell leukemia, although its role in NK-cell malignancies is unclear. Introduction of the STAT5BN642H mutation into human NK-cell lines enhances their potential to induce leukemia in mice. We have generated a mouse model that enables tissue-specific expression of STAT5BN642H and have selectively expressed the mutated STAT5B in hematopoietic cells (N642Hvav/+) or exclusively in NK cells (N642HNK/NK). All N642Hvav/+ mice rapidly develop an aggressive T/NKT-cell leukemia, whereas N642HNK/NK mice display an indolent NK-large granular lymphocytic leukemia (NK-LGLL) that progresses to an aggressive leukemia with age. Samples from patients with NK-cell leukemia have a distinctive transcriptional signature driven by mutant STAT5B, which overlaps with that of murine leukemic N642HNK/NK NK cells. To our knowledge, we have generated the first reliable STAT5BN642H-driven preclinical mouse model that displays an indolent NK-LGLL progressing to aggressive NK-cell leukemia. This novel in vivo tool will enable us to explore the transition from an indolent to an aggressive disease and will thus permit the study of prevention and treatment options for NK-cell malignancies
Diverse Listeria monocytogenes in-house clones are present in a dynamic frozen vegetable processing environment
Listeria (L.) monocytogenes is of global concern for food safety as the listeriosis-causing pathogen is widely distributed in the food processing environments, where it can survive for a long time. Frozen vegetables contaminated with L. monocytogenes were recently identified as the source of two large listeriosis outbreaks in the EU and US. So far, only a few studies have investigated the occurrence and behavior of Listeria in frozen vegetables and the associated processing environment.
This study investigates the occurrence of L. monocytogenes and other Listeria spp. in a frozen vegetable processing environment and in frozen vegetable products. Using whole genome sequencing (WGS), the distribution of sequence types (MLST-STs) and core genome sequence types (cgMLST-CT) of L. monocytogenes were assessed, and in-house clones were identified. Comparative genomic analyses and phenotypical characterization of the different MLST-STs and isolates were performed, including growth ability under low temperatures, as well as survival of freeze-thaw cycles.
Listeria were widely disseminated in the processing environment and five in-house clones namely ST451-CT4117, ST20-CT3737, ST8-CT1349, ST8-CT6243, ST224-CT5623 were identified among L. monocytogenes isolates present in environmental swab samples. Subsequently, the identified in-house clones were also detected in product samples. Conveyor belts were a major source of contamination in the processing environment. A wide repertoire of stress resistance markers supported the colonization and survival of L. monocytogenes in the frozen vegetable processing facility. The presence of ArgB was significantly associated with in-house clones. Significant differences were also observed in the growth rate between different MLST-STs at low temperatures (4 °C and 10 °C), but not between in-house and non-in-house isolates. All isolates harbored major virulence genes such as full length InlA and InlB and LIPI-1, yet there were differences between MLST-STs in the genomic content. The results of this study demonstrate that WGS is a strong tool for tracing contamination sources and transmission routes, and for identifying in-house clones. Further research targeting the co-occurring microbiota and the presence of biofilms is needed to fully understand the mechanism of colonization and persistence in a food processing environment
Mixed ensiling with by-products and silage additives significantly valorizes drought-impaired whole-crop corn
Corn silages constitute an important roughage in diets for high-yielding dairy cows. Due to summer droughts, quantity and quality of corn silages diminish, which both can have drastic consequences on the energy and nutrient provision to dairy cows. Mixed ensiling of drought-impaired whole-crop corn with by-products may represent a promising option to valorize the nutritive value and available biomass, which has not yet received much attention. Our study analyzed the potential of mixed ensiling of drought-impaired corn with either sugar beet pulp (SBP) or wheat gluten feed (WGF), without or with the application of different silage additives, i.e., either anaerobic fungi (AF) culture supernatant, mixed ruminal fluid or lactic acid bacteria. The aim was to study the effects on the chemical composition, fermentation patterns, in vitro gas production (GP), as an indicator of digestibility, and aerobic stability of the silages. We observed an overall sufficient preservation in all silages as evidenced by low dry matter (DM) losses of 336 h), while the silage pH was significantly lower with by-product inclusion. The co-ensiling with WGF predominantly increased the crude protein content to similar to 200 g/kg DM with still low ammonia-N levels, i.e., 17 g/kg crude protein, whereas co-ensiling with SBP increased the energy level as evidenced by the in vitro GP kinetics. The application of fresh AF culture supernatant further improved the preservation success, including less ammonia-N and lower silage pH, and considerably increased the energy content of pure corn silages. Remarkably, addition of fresh AF culture supernatant also improved in vitro GP kinetics of WGF-based silages that performed less than other silages when no additives were applied. Using fresh mixed ruminal fluid showed beneficial effects on silage quality, such as lower ammonia-N concentrations in all silages, whereas heat-inactivated mixed ruminal fluid decreased silage pH. For the application of lactic acid bacteria, our results showed their support in facilitating roughage preservation, but without influence on chemical composition or in vitro rumen fermentation. In conclusion, mixed ensiling with by-products is yet an overlooked option for valorizing drought-impaired corn and our data confirmed the effectiveness of this approach. Without increasing the feed-food competition, mixed ensiling represents a promising adaptation strategy to summer droughts, especially in combined use with AF culture supernatant. Future research may now investigate the impact of feeding mixed silages on performance, behavior, and health of dairy cows
Macromineral, micromineral and metal concentration of bovine colostrum samples from Salzburg, Austria
Background
Besides immunoglobulins which are essential for the calf to prevent Failure of Transfer of Passive Immunity (FTPI) colostrum contains multiple other constituents such microminerals, macrominerals and metals. The concentration of the minerals seems to be higher in colostrum than in normal milk. The aims of this study were to describe macromineral, micromineral and metal concentration of bovine colostrum samples from Salzburg, Austria and to see if there are differences in the concentrations between different cow feeding strategies and farm locations.
Methods
Therefore, 1050 individual colostrum samples were collected from 72 dairy farms from different districts of Salzburg. All colostrum samples were analysed for macromineral (K, Mg, Na), micromineral (Co, Cu, Fe, I, Mg, Se, Zn) andmetal (As, Ba, Cd, Li, Mo, Ni, Pb, Sr, Tl, U) concentrations by inductive coupled plasma mass spectrometry.
Results
The mean K, Mg and Na levels were 1218.71 mg l-1, 245.44 mg l-1 and 358.62 mg l-1, respectively. The micromineral concentrations of I, Se, Co and Zn were significantly higher in colostrum from dairy cows feeding a Total-Mixed-Ration during the lactation period in comparison to cows receiving microminerals by hand feeding, transponder feeding or via a licking bucket or licking stone. The metal analysis showed that in three farms, most of the colostrum samples showed Pb levels above the limit of 5 µg l-1.
Implications
Herd-level factors need to be addressed to elevate micromineral concentrations and to reduce metal concentrations in colostrum from dairy cows from Salzburg, Austria.
Conclusion
The results show that the macrominerals K, Mg and Na are within the range of published concentrations. For the microminerals, Co, Cu, Fe, I, Mg, Se and Zn the concentrations were significantly different depending on the mineral feeding strategies during the lactation and dry period. Metal concentrations of As, Ba, Cd, Li, Mo, Ni, Pb, Sr, Tl and U differed between the districts of Salzburg
Involvement of somatotrophic hormones in the postpartum regulation of ovarian activity in mares
Mares resume ovarian activity rapidly after foaling. Besides follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the pituitary synthesizes prolactin and growth hormone which stimulate insulin-like growth factor (IGF) synthesis in the liver. We tested the hypothesis that follicular growth is initiated already antepartum, mares with early and delayed ovulation differ in IGF-1 release and that there is an additional IGF-1 synthesis in the placenta. Plasma concentrations of LH, FSH, IGF-1, IGF-2, activin and prolactin. IGF-1, IGF-2, prolactin and their receptors in placental tissues were analyzed at the mRNA and protein level. Follicular growth was determined from 15 days before to 15 days after foaling in 14 pregnancies. Mares ovulating within 15 days postpartum formed group OV (n=5) and mares not ovulating within 15 days group NOV (n=9). Before foaling, follicles with a diameter >1 cm were present in all mares and their number increased over time (p<0.05). Follicle growth after foaling was more pronounced in OV mares (day p<0.001, group p<0.05, day x group p<0.05) in parallel to an increase in LH concentration (p<0.001, day x group p<0.001) while FSH increased (p<0.001) similarly in both groups. Plasma concentrations of IGF-1 and prolactin peaked one day after foaling (p<0.001). The IGF-1 mRNA abundance was higher in the allantochorion but lower in the amnion of OV versus NOV mares (group p=0.01, localization x group p<0.01). The IGF-1 receptor mRNA was most abundant in the allantochorion (p<0.001) and IGF-1 protein was expressed in placental tissue without differences between groups. In conclusion, follicular growth in mares is initiated before foaling and placental IGF-1 may enhance resumption of ovulatory cycles
Comparative genomics of Ascetosporea gives new insight into the evolutionary basis for animal parasitism in Rhizaria
Ascetosporea (Endomyxa, Rhizaria) is a group of unicellular parasites infecting aquatic invertebrates. They are increasingly being recognized as widespread and important in marine environments, causing large annual losses in invertebrate aquaculture. Despite their importance, little molecular data of Ascetosporea exist, with only two genome assemblies published to date. Accordingly, the evolutionary origin of these parasites is unclear, including their phylogenetic position and the genomic adaptations that accompanied the transition from a free-living lifestyle to parasitism. Here, we sequenced and assembled three new ascetosporean genomes, as well as the genome of a closely related amphizoic species, to investigate the phylogeny, origin, and genomic adaptations to parasitism in Ascetosporea.Using a phylogenomic approach, we confirm the monophyly of Ascetosporea and show that Paramyxida group with Mikrocytida, with Haplosporida being sister to both groups. We report that the genomes of these parasites are relatively small (12-36 Mb) and gene-sparse (~ 2300-5200 genes), while containing surprisingly high amounts of non-coding sequence (~ 70-90% of the genomes). Performing gene-tree aware ancestral reconstruction of gene families, we demonstrate extensive gene losses at the origin of parasitism in Ascetosporea, primarily of metabolic functions, and little gene gain except on terminal branches. Finally, we highlight some functional gene classes that have undergone expansions during evolution of the group.We present important new genomic information from a lineage of enigmatic but important parasites of invertebrates and illuminate some of the genomic innovations accompanying the evolutionary transition to parasitism in this lineage. Our results and data provide a genetic basis for the development of control measures against these parasites
The Effect of Rearing and Adult Environment on HPA Axis Responsivity and Plumage Condition in Laying Hens
The hypothalamic-pituitary-adrenal (HPA) axis responsivity is influenced by early life experience and also modified by the environment an individual experiences as an adult. Because laying hens are transferred from rearing to laying farms at 16-18 weeks of age, they are well suited to study the interaction effect between early (rearing) and adult (laying) environments on physiology and behaviour. In the European Union, there is a move towards cage-free systems for laying hens, but globally, the majority of layers are kept in conventional or furnished cages. Conventional cages have no enrichment, whereas furnished cages have little enrichment. Both cage types limit the movement of birds and the expression of highly motivated behaviours. Lack of enrichment may lead to under-stimulated birds that are more sensitive to stress and fear-inducing challenges later in life. Fearfulness has been linked to feather pecking, which has negative consequences for animal welfare and productivity. Previous research has shown that birds reared in cages are more fearful and perform more poorly in a test of spatial cognition than birds reared in aviaries when tested within five weeks after transition to adult housing. However, recent results suggest that these effects might not be long-lasting. We, therefore, tested the effect of the early (rearing) (aviary vs. cage) and adult (laying) environments (standard vs. additionally enriched furnished cages) on the corticosterone response to restraint in birds that were 35 weeks into lay (i.e., 52 weeks of age) and assessed their plumage condition. We hypothesised that a lower level of enrichment, both during rearing and adulthood, would represent a lower level of stimulation, resulting in a stronger corticosterone response to restraint and poorer feather cover. Both stressed (restrained) and control birds increased their corticosterone levels from the first (baseline) to second sample (p< 0.01 for both), but the increase in the restrained group was significantly higher than in the control group (F1, 111 = 9.51; p = 0.003). There was no effect of the early environment, but birds housed in standard furnished cages as adults had overall higher corticosterone levels than birds housed in enriched furnished cages regardless of their early life environment (F1, 51 = 4.12; p = 0.048). Neither early nor adult housing influenced the feather score except for on the belly, where birds housed in enriched cages as adults had a poorer feather score, contrary to our prediction. In conclusion, no effect of the early environment on HPA axis responsivity to an acute stressor could be detected at 52 weeks of age, but adult enrichment had a favourable effect on overall corticosterone levels