Quantitative trait Loci influencing abdominal fat deposition and functional variability of the HPA axis in the rat.

With the aim to reveal common genomic regions influencing phenotypes related to HPA axis function and metabolism, we did a quantitative trait loci (QTL) study in a F2 population obtained from the cross-breeding between 2 contrasted rat strains, LOU/C and Fischer 344. QTL determining phenotypes related first to corticotropic function were searched: plasma corticosterone (Cort) in control and stress conditions, after a dexamethasone suppression treatment (glucocorticoid receptor related-effect), and mineralocorticoid receptor-mediated urinary response to aldosterone. Then, phenotypes related to metabolism were studied on the same animals: body composition, basal and post-insulin plasma glucose, plasma free fatty acids, leptin, and insulin. Finally, we analyzed the overlapping regions between these QTL and looked for candidate genes within these regions. The gene NR3C1 encoding the glucocorticoid receptor was confirmed to be central in the link between hypothalamic-pituitary-adrenal (HPA) axis function and fat deposition, and its metabolic consequences. Among the other candidate genes detected, most contain a glucocorticoid responsive element, strengthening our hypothesis of common genetic determinism between HPA axis and metabolism.

Animal board invited review: Improving animal health and welfare in the transition of livestock farming systems: Towards social acceptability and sustainability.

The need to integrate more clearly societal expectations on livestock farming has led the authors of this article to consider that livestock farming systems must be redesigned to position health and welfare at the heart of their objectives. This article proposes a vision of the advances in knowledge required at different scales to contribute to this transformation. After defining health and welfare of animals, the article emphasises the need to consider health in a broader perspective, to deepen the question of positive emotional experiences regarding welfare, and raises the question of how to assess these two elements on farms. The positive interactions between health and welfare are presented. Some possible tensions between them are also discussed, in particular when improving welfare by providing a more stimulating and richer environment such as access to outdoor increases the risk of infectious diseases. Jointly improving health and welfare of animals poses a number of questions at various scales, from the animal level to the production chain. At the animal level, the authors highlight the need to explore: the long-term links between better welfare and physiological balance, the role of microbiota, the psycho-neuro-endocrine mechanisms linking positive mental state and health, and the trade-off between the physiological functions of production, reproduction and immunity. At the farm level, in addition to studying the relationships at the group level between welfare, health and production, the paper supports the idea of co-constructing innovative systems with livestock farmers, as well as analysing the cost, acceptability and impact of improved systems on their working conditions and well-being. At the production chain or territory levels, various questions are raised. These include studying the best strategies to improve animal health and welfare while preserving economic viability, the labelling of products and the consumers' willingness to pay, the consequences of heterogeneity in animal traits on the processing of animal products, and the spatial distribution of livestock farming and the organisation of the production and value chain. At the level of the citizen and consumer, one of the challenges is to better inter-relate sanitary and health perspectives on the one hand, and welfare concerns on the other hand. There is also a need to improve citizens' knowledge on livestock farming, and to develop more intense and constructive exchanges between livestock farmers, the livestock industry and citizens. These difficult issues plead for interdisciplinary and transdisciplinary research involving various scientific disciplines and the different stakeholders, including public policy makers through participatory research.

A major quantitative trait locus influences hyperactivity in the WKHA rat.

The syndrome of hyperactivity describes behavioural disorders existing mainly in children and characterized by increased levels of motor activity, inattention and impulsivity. Overall the aetiology is poorly understood due to the heterogeneity of the pathology although psychological, biological and social factors acting singly or in concert are generally thought to be involved. In animal studies the observed hyperactivity phenotype results from relative participation of exploration, emotionality and general activity. Studies using brain lesions, neuropharmacology and gene knock-out strategies have shown that specific elements of the brain dopaminergic system can subserve hyperactivity. Evidence of a genetic contribution comes from family and twin studies but also from the ability to select divergent animal lines on the basis of their differential activity. The Wistar-Kyoto (WKY) and Wistar-Kyoto hyperactive (WKHA) rats are such strains--distinct for their low and high activity scores in a novel environment, respectively. Here, we report the detection of a major hyperactivity-related QTL on chromosome 8, explaining 29% of the variance of an intercross between these strains. This study represents the first behavioural QTL analysis in rat and provides a new starting point for biologically categorizing different forms of hyper-activity.

Inter-strain differences in glucocorticoid and mineralocorticoid effects on macrophage and lymphocyte functions in mice.

We showed previously and we confirm here that macrophages from three mouse strains are differentially sensitive to the inhibition of expression of key inflammatory proteins (iNOS-II, IL-1 beta) by dexamethasone, a specific glucocorticoid receptor agonist (C57BL/6>DBA/2>BALB/c). Here we show that aldosterone (a specific mineralocorticoid agonist) has no effect on iNOS-II or IL-1 beta expression in macrophages from these mouse strains but decreases IL-1ra expression, with small inter-strain differences. This mechanism may be involved in the pro-inflammatory effect of this hormone. Concanavalin A-stimulated lymphocytes proliferation is also differentially sensitive to dexamethasone according to the strain, but insensitive to aldosterone.

[Involvement of hypothalamopituitary adrenal axis in abdominal obesity]. / Place de l'axe corticotrope dans le développement de l'obésité abdominale.

Obesity is increasing worldwide. Abdominal obesity, which is due to the development of visceral adipose tissue, leads to metabolic disorders. Because abdominal obesity is associated with Cushing syndrome, many studies have been performed to find out how the hypothalamopituitary adrenal axis is involved in this disorder. Here, we propose to review these data before giving our experience on changes in hypothalamopituitary adrenal axis activity regarding fat mass distribution in prepubertal children.

Marked genetic differences in the regulation of blood glucose under immune and restraint stress in mice reveals a wide range of corticosensitivity.

Male and female mice from different control strains (C57BL/6, DBA/2, BALB/c) and the nonobese diabetic (NOD) strain, a spontaneous model of type 1 diabetes, were subjected to various stressors (restraint, lipopolysaccharide or interleukin-1 injection). Significant differences were measured among strains in blood glucose, insulin and corticosterone levels and, for restraint, IL-6. Addition of dexamethasone, a glucocorticoid receptor agonist, to inhibit the expression of several proteins by LPS-stimulated bone marrow-derived macrophages in vitro showed a gradient among control strains: C57BL/6>DBA/2>BALB/c corroborating the pattern of corticosensitivity suggested by their stress-induced glucose responses at the systemic level.

Seasonal effects on plasma cortisol concentrations in the Bedouin buck: circadian studies and response to ACTH.

Our work aims at the exploration of cortisol secretion in the Bedouin goat, native to the Algerian Sahara desert, to understand the mechanisms of adaptation to extreme hot climates. In the present study, diurnal and seasonal variations of cortisol concentrations were measured in basal conditions, as well as the response to ACTH stimulation tests across seasons in bucks. The plasma concentrations of cortisol showed no diurnal cycle but a large variation across seasons. The highest levels occurred in summer and winter when the environmental conditions are at their extreme levels. The rectal temperature showed nychthemeral and seasonal variations, and BW was also different across seasons with highest values in summer and lowest in winter. The results obtained after administration of two doses (2 or 10 µg/kg BW) of synthetic ACTH to three different age groups (kids, adults and elderly animals) showed a strong increase in plasma cortisol concentrations under all conditions with maximum levels achieved between 15 and 120 min. The analysis of the area under the cortisol curve showed no significant difference between the responses to the two doses of ACTH and between age groups, but showed seasonal variations with the lowest response in autumn than in other seasons. We conclude that season significantly affects secretion of cortisol in both basal state and under ACTH stimulation. However, the variation of adrenal reactivity to ACTH is not sufficient to explain seasonal differences, and in particular the summer peak in basal circulating cortisol concentrations. Further research should focus on the respective contribution of environmental factors (such as day length, temperature, humidity) and the mechanisms involved in cortisol regulation.

Review: divergent selection for residual feed intake in the growing pig.

This review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant (P<0.001) line differences for RFI (-165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (-270 g/day). Low responses were observed on growth rate (-12.8 g/day, P<0.05) and body composition (+0.9 mm backfat thickness, P=0.57; -2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (-0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat (P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (-10% after five generations of selection) and activity (-21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors, via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory.

Evidence for a female-specific effect of a chromosome 4 locus on anxiety-related behaviors and ethanol drinking in rats.

Previous studies using the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR) led to the mapping of two quantitative trait loci, named Ofil1 (on chromosome 4 of the rat) and Ofil2 (on chromosome 7), for open-field inner locomotion, a behavioral index of anxiety. Studies using other strains showed that the region next to Ofil1 influences measures of not only anxiety but also ethanol consumption. In view of the high prevalence of psychiatric disorders such as anxiety and alcoholism, as well as the comorbidity between them, the present study was designed to better characterize the contribution of these two loci to complex emotional and consummatory responses. Rats deriving from an F2 intercross between the LEW and the SHR strains were selected according to their genotype at markers flanking the loci Ofil1 and Ofil2 and bred to obtain lines of rats homozygous LEW/LEW or SHR/SHR for each of the two loci, thus generating four genotypic combinations. These selected animals as well as purebred LEW and SHR rats of both sexes were submitted to a battery of tests including measures of locomotor activity, anxiety, sweet and bitter taste reinforcement and ethanol intake. Lewis rats displayed more anxiety-like behavior and less ethanol intake than SHR rats. Ofil1 (on chromosome 4) affected both the activity in the center of the open field and ethanol drinking in females only. These results suggest that Ofil1 contains either linked genes with independent influences on anxiety-related responses and ethanol drinking or a pleiotropic gene with simultaneous effects on both traits.

Validation of a behavioral observation tool to assess pig welfare.

Accurately measuring and monitoring of animal behavior is an important factor when assessing on-farm animal welfare. First we developed a feasible and simple method aiming at consistently on-farm measuring of pig's behavior. This test should cover a broad range of welfare-related pig behavior. The reaction towards a novel object, startling, tail and ear biting, play and aggressive behavior, stereotypies, coughing, sneezing, skin lesions, defecation, urination and cleanliness of body and pen are included. The development of accurate measures of on-farm behavior first requires the reliability assessment of the procedure. Therefore, the methodology was tested in a first part by three observers scoring simultaneously and independently pre-defined behavioral characteristics of 108 group-housed fattening pigs. The inter-observer repeatability of the measures was calculated using intraclass correlation coefficients, which ranged from 0.7 to 1. In a second part, the objective was to validate the behavioral characteristics against salivary cortisol, urinary epinephrine and norepinephrine and production traits. Salivary cortisol concentrations significantly increased in ear-bitten pigs and in pigs with tail lesions. Growth rate significantly dropped when cortisol levels rose. An age effect was also found. The percentage of animals approaching the novel object is positively correlated with the urinary epinephrine concentration. Pigs defecating during the test showed significantly higher epinephrine levels. Urinary norepinephrine concentration decreased significantly with age. Faster growing animals and animals with tail lesions showed significantly higher levels of norepinephrine. Pen dirtiness and number of animals per pen were associated with higher norepinephrine concentrations. Finally, barrows had higher norepinephrine concentrations than sows.

Effect of feed texture, meal frequency and pre-slaughter fasting on carcass and meat quality, and urinary cortisol in pigs.

Carcass and meat quality traits, and urinary cortisol variation was studied in 96 barrows assigned to the following treatments: feed texture (FT; mash vs. pellets), meal frequency (MF; 2 vs. 5 meals per day) and fasting time (F; 4, 14 and 24h) according to a 2×2×3 factorial design. Pigs fed mash, receiving feed five times a day and fasted for 24h before slaughter had lower carcass dressing yield (P<0.001). A higher (P<0.05) bruise score was found on carcasses from pigs fasted for 14 and 24h and fed either pelleted or mashed feed five times per day. The pH(u) value in the Longissimus muscle increased (P<0.05) with increasing fasting time, whereas in the Adductor muscle it was higher (P<0.05) in pigs fed with pellets in two meals per day and fasted for 24h. Urinary cortisol tended to be higher in pigs fasted for 14h compared to those fasted for 4 (P=0.10) and 24h (P=0.06). The results of this study show a significant influence of pellet feeding on carcass yield in fasted pigs, while the effects of pre-slaughter fasting time on meat quality traits were limited.

Interplay between aggression, brain monoamines and fur color mutation in the American mink.

Domestication of wild animals alters the aggression towards humans, brain monoamines and coat pigmentation. Our aim is the interplay between aggression, brain monoamines and depigmentation. The Hedlund white mutation in the American mink is an extreme case of depigmentation observed in domesticated animals. The aggressive (-2.06 ± 0.03) and tame (+3.5 ± 0.1) populations of wild-type dark brown color (standard) minks were bred during 17 successive generations for aggressive or tame reaction towards humans, respectively. The Hedlund mutation was transferred to the aggressive and tame backgrounds to generate aggressive (-1.2 ± 0.1) and tame (+3.0 ± 0.2) Hedlund minks. Four groups of 10 males with equal expression of aggressive (-2) or tame (+5) behavior, standard or with the Hedlund mutation, were selected to study biogenic amines in the brain. Decreased levels of noradrenaline in the hypothalamus, but increased concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid and dopamine metabolite, homovanillic acid, in the striatum were measured in the tame compared with the aggressive standard minks. The Hedlund mutation increased noradrenaline level in the hypothalamus and substantia nigra, serotonin level in the substantia nigra and striatum and decreased dopamine concentration in the hypothalamus and striatum. Significant interaction effects were found between the Hedlund mutation and aggressive behavior on serotonin metabolism in the substantia nigra (P < 0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the striatum (P < 0.05). These results provide the first experimental evidence of the interplay between aggression, brain monoamines and the Hedlund mutation in the American minks.

Feather pecking in chickens is genetically related to behavioural and developmental traits.

Feather pecking (FP) is a detrimental behaviour in chickens, which is performed by only some individuals in a flock. FP was studied in 54 red junglefowl (ancestor of domestic chickens), 36 White Leghorn laying hens, and 762 birds from an F(2)-intercross between these two lines. From all F(2)-birds, growth and feed consumption were measured. Age at sexual maturity and egg production in females, and corticosterone levels in males were also measured. From 333 F(2)-birds of both sexes, and 20 parental birds, body composition with respect to bone mineral content, muscle and fat was obtained by post-mortem examinations using Dual X-Ray Absorptiometry (DXA). In femurs of the same birds, the bone density and structure were analysed using DXA and Peripheral Quantitative Computerized Tomography (pQCT), and a biomechanical analysis of bone strength was performed. Furthermore, plumage condition was determined in all birds as a measure of being exposed to feather pecking. Using 105 DNA-markers in all F(2)-birds, a genome-wide scan for Quantitative Trait Loci (QTL), associated with the behaviour in the F(2)-generation was performed. FP was at least as frequent in the red junglefowl as in the White Leghorn strain studied here, and significantly more common among females both in the parental strains and in the F(2)-generation. In the F(2)-birds, FP was phenotypically linked to early sexual maturation, fast growth, weak bones, and, in males, also high fat accumulation, indicating that feather peckers have a different resource allocation pattern. Behaviourally, F(2) feather peckers were more active in an open field test, in a novel food/novel object test, and in a restraint test, indicating that feather pecking might be genetically linked to a proactive coping strategy. Only one suggestive QTL with a low explanatory value was found on chromosome 3, showing that many genes, each with a small effect, are probably involved in the causation of feather pecking. There were significant effects of sire and dam on the risk of being a victim of feather pecking, and victims grew faster pre- and post-hatching, had lower corticosterone levels and were less active in a restraint test. Hence, a wide array of behavioural and developmental traits were genetically linked to FP.

Stress hormones, carcass composition and meat quality in Large White×Duroc pigs.

The levels of stress hormones, cortisol and catecholamines (adrenaline and noradrenaline), were measured in urine collected after slaughter from the bladder, in 309 pigs (females and castrated males) from an F2 intercross between the Large White and Duroc breeds to analyze the relationships between stress-responsive neuroendocrine systems, carcass composition and meat quality. Intramuscular fat content was measured from a biopsy sample taken at a live weight of 70 kg from the longissimus lumborum muscle, and carcass and meat quality traits were also collected. Carcass fat content was higher and estimated carcass lean meat content was lower with increasing urinary levels of cortisol and adrenaline (that are highly correlated with each other), but was not related to the levels of noradrenaline, showing that adrenal hormones favor the accretion of fat at the expense of muscle proteins, a typical physiological effect of cortisol. On the contrary, intramuscular fat levels were unrelated to either hormone level. Finally, muscle pH measured 24 h after death was positively correlated with catecholamine levels, an effect related to the catabolism of muscle glycogen by catecholamines released by preslaughter stress, which impairs post-mortem acidification of meat. These results show the importance of a control over stress neuroendocrine systems to increase pork production and product quality, and the value of the genetic approach to reach this goal.

Quality pork genes and meat production.

Functional genomics, including analysis of the transcriptome and proteome, provides new opportunities for understanding the molecular processes in muscle and how these influence its conversion to meat. The Quality Pork Genes project was established to identify genes associated with variation in different aspects of raw material (muscle) quality and to then develop genetic tools that could be utilized to improve this quality. DNA polymorphisms identified in the porcine PRKAG3 and CAST genes illustrate the impact that such tools can have in improving meat quality. The resources developed in Quality Pork Genes provide the basis for identifying more of these tools.

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin.

In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1-24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r p=0.539; genetic correlation, r g=0.938). Post-ACTH cortisol levels were highly heritable (h 2=0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but also point at pigs as a relevant model to explore the underlying mechanisms of the metabolic syndrome including the contribution of genetic factors.

Stress and emotionality: a multidimensional and genetic approach.

The use of behavioural tests aiming to assess the psychological components of stress in animals has led to divergent and sometimes arbitrary interpretations of animal behaviour. This paper presents a critical evaluation of behavioural methods currently used to investigate stress and emotionality. One of its main goals is to demonstrate, through experimental evidence, that emotionality may no longer be seen as a unidimensional construct. Accordingly, following a discussion about concepts, we propose a multiple-testing approach, paralleled by factor analyses, as a tool to dissociate and study the different dimensions of emotionality. Within this multidimensional context, genetic studies (illustrated here by different rat models) are shown to be particularly useful to investigate the neurobiology of stress/emotionality. A genetic approach can be used (i) to broaden and dissect the variability of responses within and between populations and (ii) to search for the molecular bases (i.e. genes and gene products) which underlie such a variability.

Estrogens, cyclic adenosine 3',5'-monophosphate, and phorbol esters modulate the prolactin response of GH3 cells to basic fibroblast growth factor.

The effects of basic fibroblast growth factor (bFGF) on the secretion of PRL and GH by a cell line derived from a rat pituitary tumor (GH3 cells) were examined. The interactions between bFGF and compounds that are known to modify the activity of GH3 cells (estradiol, cAMP, and phorbol esters) were also studied. bFGF has little effect on cell growth or on the secretion of GH by GH3 cells but specifically increases the capacity of the cells to release PRL. The effect is time and dose dependent and reaches maximal levels with a 24-h preincubation of the cells with bFGF. The effects of bFGF on PRL secretion are potentiated by the addition of estradiol (maximally effective dose 100 pg/ml approximately 10(-10) M) and are further increased by the addition of the phorbol ester, phorbol myristate acetate. The results indicate that, like in normal lactotrophs, bFGF has a major influence on the release of PRL by tumor-derived GH3 cells. The results support the hypothesis that bFGF may play an important paracrine, if not autocrine, role in regulating the PRL-secreting cells of the pituitary. The potential use of GH3 cells to elucidate the mechanism through which bFGF modulates differentiated cell function is discussed.

Studies of the nature of the interaction between vasopressin and corticotropin-releasing factor on adrenocorticotropin release in the rat.

Arginine-vasopressin (AVP) acts on vasoconstriction and diuresis through two different types of receptors (V1 and V2, respectively). Since AVP also modifies ACTH release, we have attempted to determine which class of receptors mediates the capacity of AVP to increase ACTH secretion and to potentiate the effect of corticotropin-releasing factor (CRF) on the pituitary using two AVP antagonists: [1-deaminopenicillamine-2-(O-methyl)tyrosine]arginine-vasopressin [dPTyr(Me)-AVP], which blocks V1 receptors, and [1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid)2-D-leucine-4-valine]arginine vasopressin [d(CH2)5DLeuValAVP], which interferes with V2 receptors. dPTyr(Me)AVP, but not d(CH2)5DLeuValAVP, inhibited the ACTH-releasing as well as the CRF-potentiating effects of both AVP and its antidiuretic analog [1-deamino-8-D-arginine]vasopressin (dDAVP). These results suggest that the actions of AVP and dDAVP on the corticotrophs is primarily mediated through V1 (pressor-like) receptors.

Psychosocial stress can induce chronic hypertension in normotensive strains of rats.

We report on five 6-month experiments during which five colonies of four male and four female rats were exposed to psychosocial stress. Monthly blood pressure measurements by a tail-cuff method showed a modest (10 mm Hg) increase in two studies using Sprague-Dawley rats. In two further studies using the more aggressive Long-Evans strain, terminal direct carotid arterial pressures were taken as well, and in one study the differences exceeded 20 mm Hg. A fifth study used the Wistar-Kyoto, hyperactive (WKHA) strain developed by Hendley, and no differences were observed. Heart and adrenal weights; adrenal catecholamine synthetic enzymes; and heart, aortic, and kidney histology were measured and showed significant changes, which for the most part paralleled blood pressure changes. Social instability and the associated blood pressure changes were made more severe by periodic mixing of males from different colonies. This had no effect on the peaceable WKHA rats, some effect on the Sprague-Dawley rats, and a severe effect on the Long-Evans rats. The WKHA rats failed to show blood pressure changes despite stress-induced increases in heart and adrenal weights. Thus, different types of psychosocial stress and different genetics combine to induce a variety of neuroendocrine changes, not all of which necessarily lead to increased blood pressure.