Colony Of Rats Research Articles

In vivo fertilization improved the cryotolerance and developmental ability of vitrified-warmed rat fertilized oocytes

The cryopreservation of rat embryos is useful for efficiently archiving rat resources in bioresource repositories. The cryopreserved fertilized oocytes can be quickly reanimated to rats with homozygous mutations using embryo transfer. In addition, cryopreserved rat fertilized oocytes are easier to transport than live animals. Before cryopreservation, fertilized oocytes are obtained by mating or in vitro fertilization. However, it is not clear which fertilized oocytes are most suited to cryopreservation. In this study, we performed a systematic comparison of the fertilizing ability, cryotolerance, and developmental ability of cryopreserved fertilized oocytes at the pronuclear stage produced either by mating (in vivo) or in vitro fertilization (in vitro) in SD and F344 rats. In vivo-fertilized oocytes had higher cryotolerance and developmental ability than in vitro-fertilized oocytes in SD and F344 rats. Furthermore, the fertilization ability, cryotolerance, and developmental ability of vitrified-warmed fertilized oocytes differed between SD and F344 rats. In conclusion, our study suggests that in vivo-fertilized rat oocytes were more suitable for cryopreservation. Our protocol provides an optimized system for the management of rat colonies using fertilized oocytes cryopreservation and contributes to the 3Rs principle by reducing the number of animals used for research.

Do Frequent Lactation Periods in Laboratory Rat Colonies Have a Negative Effect on Mothers' Care and Feeding of Themselves and Their Offspring?

Laboratory rats are the second most preferred mammal species in experimental research. Do the frequent lactation periods of the female rats used in production in this study negatively affect the care of the offspring and themselves? For this purpose, the care of mother rats from a conventional outbred Wistar Albino rat colony for themselves and their offspring was monitored in two consecutive lactation periods. Mother rats successfully raised all their offspring in two lactation periods, mothers spent 85% of their daily life in the early phase of the two lactation periods (Post Natal-PN 1-8 days), 60% of their daily life in the mid-lactation phase (PN 9-18 days) and 60% of their daily life in the late lactation phase (PN 19-23 days) have been found to spend 30% of their daily lives with their offspring. While there was a significant difference in terms of the times that mother rats were with their babies in the early, middle, and late stages of the lactation period, the time they were separated from their babies and the frequency of separation (p< .001), no significant difference was found when the same stages of the two lactation periods were compared with each other (p> .05). Live weight change, feed consumption, and water consumption changes of mother rats in two lactation periods were compared and no significant difference was found. It was concluded that there was no negative effect on the care of mother rats and their offspring during frequent lactation periods.

Positive effect of a diggable substrate on the behaviour of a captive naked mole rat colony

Naked mole rats (Heterocephalus galber) are eusocial mammals from East Africa. Their extraordinary social organisation is accompanied by remarkable adaptations to an underground lifestyle, extreme longevity and resistance to many diseases, making naked mole rats a highly relevant model for biological research. However, their living conditions in controlled environments do not allow them to express fundamental behaviours: digging galleries and exploring. This gap probably constitutes a bias to any behavioural or even medical study, because it represents a potential obstacle to their well-being. In this article, we tested the effects of the introduction of a diggable substrate on the behaviour of a colony of naked mole rats at the Menagerie, le Zoo du Jardin des Plantes, Paris. We measured individual exploratory latencies, the number of entries per minute and the frequency with which naked mole rats gnawed tunnels during observation trials. We found that: (i) young individuals explore more quickly, (ii) the introduction of a diggable substrate encourages exploration and digging behaviour, and (iii) could therefore be a relevant element to introduce under human care. This new environmental design could improve the welfare of naked mole rats by creating opportunities for cognitive challenges such as exploration and environmental control.

When are females dominant over males in rats (Rattus norvegicus)?

In group-living animals, males are assumed to be dominant over females when they are larger than females. Despite this, females have sometimes been proven to be dominant over some males via the winner-loser effect, which becomes stronger when the intensity of aggression in the group is higher. To test whether the winner-loser effect leads to (partial) female dominance in a species with a pronounced sexual dimorphism, we studied the hierarchy in 12 rat colonies (Rattus norvegicus) in which the rats could freely interact with their group members within a spacious area. To investigate the underlying mechanisms, we compared the empirical data to hypotheses generated by the agent-based model ‘DomWorld’. We show that females dominated on average 55% of the males, and occupied the alpha position in four colonies, in three of them they shared it with one or several males. Moreover, in line with the predictions of the computational model, females dominated a higher percentage of males when the intensity of aggression of the colony was higher. This shows that although females are only half as heavy as males, they dominate part of the males probably through the winner-loser effect. We suggest that this effect may be widespread in many other species and can be tested experimentally.Significance statementIt is often assumed that males automatically dominate females because males are bigger and stronger than females in many species. However, the present study shows that females can dominate males due to the winner-loser effect. We used an agent-based computational model to generate specific hypotheses that we empirically tested in a large sample of rat colonies. Despite this species having a pronounced male-biased sex dimorphism, some females dominated males – with one female even occupying an unshared alpha position. Such partial female dominance was stronger in colonies with higher intensity of aggression. Here, defeated males may suffer a drastic decrease in their fighting capability and consequently give females more opportunities to surpass them in the hierarchy.

Enlarged colony housing promotes linear progression of subchondral bone remodeling in joint instability rat models.

Objective: Osteoarthritis (OA) is a disease with high prevalence and an unmet medical need for disease modifying treatments. In rat models, OA-like subchondral bone and cartilage changes can be induced by instability surgery with different severity levels. Factors which determine structural changes additionally comprise the study duration and activity-impacted joint loading. Methods: A medial meniscal tear (MMT) or anterior cruciate ligament transection with partial meniscectomy (ACLT+pMx) was induced unilaterally in rats housed in a rat colony cage (RCC), allowing high activity levels including jumping and stair climbing. In parallel, ACLT+pMx rats were housed in Type IV cages. The time course of OA-related changes was investigated at 4, 8, 12, and 16weeks after surgery by micro-CT, gait analysis and joint diameter measurements. Results: Gait disturbance was observed after 2weeks and to a similar extend in all models. The increase in ipsilateral joint diameters peaked after 2weeks and were more pronounced after ACLT+pMx compared to MMT-surgery, but independent of housing. Micro-CT analysis revealed that increases in osseous tibial width were most distinct after ACLT+pMx in RCC and progressed continuously until week sixteen. In contrast, osseous tibial width of ipsilateral joints in MMT RCC and ACLT+pMx Type IV groups did not increase further after week twelve. In contralateral joints, this parameter was not affected, regardless of the model or caging. However, a significant increase in bone volume fraction and trabecular thickness was observed over time in the femur and tibia of both ipsilateral and contralateral knees. Here, the medial tibial compartment of the operated joint was most affected and linear changes were most pronounced in the ACLT+pMx RCC group. Conclusion: Increased movement of animals in colony cages leads to robust structural changes in subchondral bone after surgically induced joint instability over time, while in regular Type IV housing maximal changes are reached in week twelve. The new insights into the differentiation of the models, particularly with respect to the linear progression of bone changes in ACLT+pMx in the RCC, may be useful for the design of chronic OA-studies within a longer lifespan and therefore supporting the development of novel therapies.

Ratos e camundongos de laboratório do Brasil: décadas se passam, mas as infecções parasitárias permanecem

ABSTRACT: Rats and mice are the most used experimental models in research. Globally, animal houses are subjected to parasite outbreaks. In Brazil, the parasitological profile is used to reflect the sanitary condition of laboratory animals and must be monitored frequently. The present study developed an integrative review of scientific studies on the parasitological profile of rats and mice in animal facilities in Brazil. It identified the most prevalent parasite species reported in animal facilities from different geographic regions of the country, as well as factors contributing to the perpetuation of these parasites, and proposed measures to help prevent such infections. Based on the guiding question “which endoparasites and ectoparasites have already been identified in rat and mouse colonies in animal facilities in Brazil?” and considering inclusion and exclusion criteria, 28 studies published between 1974 and 2021 were selected in four scientific bases. These studies covered facilities in 12 Brazilian States, describing 16 genera of parasites in mice and 18 in rats. Most of the facilities in the selected studies were of the conventional type and with few sanitary barriers, and these conditions may favor the recurrence of parasites. Efforts are, therefore, necessary for institutions to have animal facilities in accordance with the legislation and practice optimal methodologies. The measures proposed in this article can contribute to change the panorama of parasites in the national animal facilities, aiming to safeguard the quality of scientific data and animal welfare.

Investigation of Microbiological, Physiological and Histopathological Changes in Polymicrobial Infection in Old Rats

Background: The aim of this study is to examine the microbiological, clinical, physiological and pathological findings of natural polymicrobial infection developing in a wistar rat colony under long-term observation. Methods: In this study, 70 male Wistar albino rats, 3 years old, raised by conventional methods and housed in a cage environment were used. Thirteen rats with clinical symptoms such as torticollis and rotation were sacrificed for microbiological and histopathological examination after 14 days. For microbiological examination, the rapid diagnostic kit BBL Crystal system was used to identify bacterial agents in tissue and stool samples, and the traditional culture method was used for isolation. Result: As a result of microbiological analysis, the rarely isolated Staphylococcus capitis (S. capitis) was isolated. Different Staphylococcus spp. It has been determined that the species can cause suppurative meningoencephalitis as well as septicemia in the brains of experimental animals., it is thought that polymicrobial infection will be useful for the identification of bacterial agents and infection prevention and treatment strategies.

Efficacy of Dynamics-based Features for Machine Learning Classification of Renal Hemodynamics.

Different machine learning approaches for analyzing renal hemodynamics using time series of arterial blood pressure and renal blood flow rate measurements in conscious rats are developed and compared. Particular emphasis is placed on features used for machine learning. The test scenario involves binary classification of Sprague-Dawley rats obtained from two different suppliers, with the suppliers' rat colonies having drifted slightly apart in hemodynamic characteristics. Models used for the classification include deep neural network (DNN), random forest, support vector machine, multilayer perceptron. While the DNN uses raw pressure/flow measurements as features, the latter three use a feature vector of parameters of a nonlinear dynamic system fitted to the pressure/flow data, thereby restricting the classification basis to the hemodynamics. Although the performance in these cases is slightly reduced in comparison to that of the DNN, they still show promise for machine learning (ML) application. The pioneering contribution of this work is the establishment that even with features limited to hemodynamics-based information, the ML models can successfully achieve classification with reasonably high accuracy.

A nude mutant rat derived from Sprague Dawley-National Institute of Nutrition rat colony with normal thymus: A potential model for noncommunicable diseases.

A spontaneous mutant rat with a hairless phenotype and an intact thymus was discovered in a long-standing Sprague Dawley-National Institute of Nutrition (SD/NIN) rat colony at a national animal resource facility. We conducted extensive phenotypic and biochemical analyses on this mutant strain to determine its suitability as a preclinical model for immunocompetent testing in noncommunicable disease research. We subjected the mutant rats to strict and frequent phenotypic and genetic surveillance to accomplish this objective. The animals were assessed for food intake, body weight, blood cell profile, clinical chemistry, adipose tissue deposition, and bone mineral density (BMD) using total electrical body conductance (TOBEC) and dual-energy X-ray absorptiometry (DXA) analysis. Initially, only two hairless mutant rats, a male and a female, were born from a single dam in the SD/NIN rat strain. However, the results indicate that the mutant colony propagated from these unique pups displayed distinct phenotypic features and exhibited differences in feeding behavior, weight gain, and clinical biochemistry. The food conversion rate was significantly higher in nude females (2.8-fold) while 26% lower in nude males. Both sexes of nude rats had significantly higher triglycerides and lower glucose levels in females. However, glucose levels did not change in male nude rats. Furthermore, nude female and male rats had significantly lower fat (TOBEC) and bone mineral content (DXA). Nonetheless, BMD was only slightly lower (7%-8%) compared to the heterozygous groups. These findings indicate that the spontaneous mutant rat has the potential to serve as an immunopotent and modulatory testing system in pharmacokinetics/pharmacodynamics and toxicology, which can be further explored for therapeutic drug discovery.

Impact of Resolvin-D1 in the resolution of atrial inflammation and arrhythmogenic cardiac remodelling in a rat model of myosin light chain 4 (MYL-4) mutation

Atrial fibrillation (AF) is the most common heart rhythm disorder. AF risk factors include age, hypertension, obesity, or myocardial infarction. AF can cause severe complications such as stroke and sudden death. Hence, AF is a major public health issue. Proteins called actins and myosins interact to allow myocardial contractions. A mutation affecting the gene encoding a myosin light chain type 4 (MYL-4) protein is associated with a genetically inheritable form of AF. Furthermore, we have recently demonstrated that MYL-4 rats develop atrial inflammation and fibrosis. Conventional anti-inflammatory medications are ineffective against AF. Bioactive endogenous autacoids, called specialized proresolving mediators, including resolvin-D1: RvD1, have been described to promoting inflammation-resolution and potentially reduce AF occurrence. To elucidate the impact of a triggered resolution of inflammation in the prevention of AF. Resolution of atrial inflammation by daily treatment with RvD1 prevents the development of AF in a rat model of MYL-4 mutation. We have developed a colony of male and female Sprague-Dawley Knock-In rats, mutated on the Myl-4 gene. A dose of 2 μg/kg/d RvD1 (or equivalent dose of vehicle) was administered to wild-type (WT) and MYL-4 rats for 21 days. AF was assessed by in vivo electrophysiological study. The structure of the atria was studied by echocardiography, histology and electron microscopy. The expression levels of proteins (by western blotting) and genes (by qPCR) involved in inflammation and cellular apoptosis have been assessed in the right and left atria of MYL-4 rats compared to WT. Compared to WT rat, MYL-4 mutation causes an increased risk of AF, associated with an inflammatory and apoptotic profile in the atria. We observed that daily treatment with RvD1 prevents atrial inflammation (IL-1β), reduces cell death (Bax, Bcl2) and attenuates atrial structural remodelling (dilation, hypertrophy). Inflammation plays a crucial role in the development of arrhythmogenic atrial remodeling observed in rats carrying MYL4 mutation. In addition, this project contributes to highlight the potential therapeutic effects of the RvD1 treatment, to resolve inflammation and prevent AF in the context of a rhythm disturbances provoked by cardiac mutations.

Late Pregnant Dahl Salt-Sensitive Rats from Charles River Laboratories Do Not Exhibit Superimposed Preeclampsia.

Healthy pregnancy is characterized by a reduction in total peripheral vascular resistance which produces a decrease in maternal blood pressure. Failure of this normal maternal adaptation to pregnancy results in hypertensive disorders of pregnancy, which are dangerous for both the mother and fetus. Recently, it has been proposed that Dahl salt-sensitive (SS) rats are a model of spontaneous superimposed preeclampsia when maintained on a normal salt diet. Since these reports are from animals that are derived from sources that are not commercially available, the purpose of this study was to evaluate the blood pressure and pregnancy outcomes of SS rats from a commercial vendor. Mean arterial blood pressure was measured by indwelling femoral catheter in anesthetized SS virgin and SS day 21 late pregnant rats from Charles River Laboratories (CRL). Fetal outcomes from SS rats and control Sprague-Dawley (SD) rats were also measured. All rats were euthanized by exsanguination under anesthesia and tissues weighed. Virgin SS rats were found to have normal mean arterial blood pressure (102 ± 2mmHg), and late pregnant SS rats had the normal decrease in maternal blood pressure. SS rats were also found to have normal pregnancy outcomes. These results suggest that SS rats from CRL are not a model of superimposed preeclampsia. Further studies will be aimed at determining the differences between the blood pressure phenotype and pregnancy outcomes of existing colonies of SS rats in order to elucidate the mechanisms permitting the development of preeclampsia in certain colonies of this strain.

Inimical impact of high-fat diet on expression of heme oxygenase-1, trace metals content, and associated intestinal histopathology.

A high-fat diet (HFD) is one of the most prominent causative factors for obesity and metabolic inflammation. The effects of HFD overconsumption on intestinal histology, expression of haem oxygenase-1 (HO-1), and transferrin receptor-2 (TFR2) remain elusive. The present study was conducted to analyze the effect of HFD on these parameters. To develop the HFD-induced obese model, rat colonies were divided into 3 groups; the control group was reared on normal rat chow, whereas groups I and II were given HFD for 16 weeks. Hematoxylin and eosin (H & E) staining revealed marked epithelial changes, inflammatory cell infiltrates, and destruction of mucosal architecture in both experimental groups as compared to the control group. Sudan Black B staining showed a high triglyceride deposition in the intestinal mucosa of animals fed on HFD. Atomic absorption spectroscopy revealed a decrease in tissue copper (Cu) and selenium (Se) concentration in both HFD experimental groups. Whereas the cobalt (Co) and manganese (Mn) levels were comparable to controls. The mRNA expression levels of HO-1 and TFR2 were found to be significantly upregulated in HFD groups compared to the control group. Hence, HFD consumption leads to histopathological changes and altered gene expression in the rodent intestine. So, one should remove HFD from daily meals to avoid related metabolic complications.

The “Second Life” of laboratory rats (Rattus norvegicus): Assessment of social behavior of a colony of rats based on social network analysis

ABSTRACT Rattus norvegicus is a social animal and holds a significant economic value, considering its use in scientific research. Here, we use the Social Network Analysis (SNA) approach to study the social interactions of a group of rats held in a post-laboratory animal care facility. We collected interaction data during four study periods, for a total of 60 days. At the group level, rats presented two communities for each study period, consisting mainly of littermates. At individual level, we found that the rats preferred to interact with individuals of the same strain and laboratory of origin and with littermates. At temporal level, we studied how stable social interactions were over time. During the first study period, we found high social stability, whereas the introduction of new individuals in the subsequent period caused social rearrangements; however, the initial social stability was restored. Our findings have shown that studying the social behavior of rats using SNA is a valuable tool for advancing our understanding of the social system of this species, which has the potential to enhance management and welfare practices.

Housing and Husbandry Alternatives for Naked Mole Rat Colonies Used in Research Settings.

Naked mole rats (Heterocephalus glaber) are a unique rodent species originating in Africa and are increasingly being used in research. Their needs and characteristics differ from those of other rodents used in research. Unique housing systems are necessary to address the special macro- and microenvironmental requirements of NMRs. Naked mole rats are one of the 2 known eusocial mammalian species, are extremely long-living, are active burrowers, and are accustomed to a subterranean environment. Unlike typical rats and mice, naked mole rats need specific, unique housing systems that mimic their natural subterranean environment to support health and longevity. Here we provide an overview of naked mole rats and a housing method that can be used in research settings.

Detection of high antibodies titers against rat leukemia virus in an outbreak of reproductive disorders and lymphomas in Wistar rats.

Young female Wistar rats from a specific pathogen free breeding colony presented an outbreak of infertility along with neurological symptoms and malignant lymphomas. We evaluated the presence and the potential role of the rat leukemia virus (RaLV) in the disease because these clinical signs could be compatible with a retrovirus. RaLV is a mammalian type C endogenous retrovirus initially isolated from in vitro Sprague-Dawley rat embryo cultures. There are no reports of clinical disease in rats associated with this virus, and little is known about its interaction with the host. Using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, we studied the synthesis of the viral particles and the development of an immune response against the virus in this rat colony. The results showed that healthy and diseased Wistar rats synthetized viral RNA but only diseased animals developed a detectable immune response against RaLV envelop protein. Furthermore, rats with lymphomas tended to have higher titers of antibodies against RaLV epitopes than those with infertility or neurological symptoms. The results suggest that increases in the RaLV infectious particle loads could be involved in the development of lymphomas in young rats. The potential causes of RaLV reactivation are discussed.

Evaluation of comparative effectiveness of different insecticides on pediculosis in Wistar rat colony naturally infested by Polyplax spinulosa - A spined rat louse

Evaluation of comparative effectiveness of different insecticides on pediculosis in Wistar rat colony naturally infested by Polyplax spinulosa - A spined rat louse

An Evaluation of Cardiac Health in the Spontaneously Hypertensive Rat Colony: Implications of Evolutionary Driven Increases in Concentric Hypertrophy.

The Spontaneously Hypertensive Rat (SHR) Colony was established in 1963 and is the most commonly used rodent model for studying heart failure (HF). Ideally, animal models should recapitulate the clinical disease as closely as possible. Any drift in a genetic model may create a new model that no longer adequately represents the human pathology. Further, instability overtime may lead to conflicting data between laboratories and/or irreproducible results. While systolic blood pressure (SBP) is closely monitored during inbreeding, the sequelae of HF (e.g., cardiac hypertrophy) are not. Thus, the object of this review was to investigate whether the hypertension-induced sequelae of HF in the SHR have remained stable after decades of inbreeding. A systematic review was performed to evaluate indices of cardiovascular health in the SHR over the past 60 years. For post hoc statistical analyses, studies were separated into 2 cohorts: Initial (mid to late 1900s) and Current (early 2000s to present) Colony SHRs. Wistar-Kyoto rats (WKY) were used as controls. SBP was consistent between Initial and Current Colony SHRs. However, Current Colony SHRs presented with increased concentric hypertrophy (i.e., elevated heart weight and posterior wall thickness) while cardiac output remained consistent. Since these changes were not observed in the WKY controls, cardiac-derived changes in Current Colony SHRs were unlikely due to differences in environmental conditions. Together, these data firmly establish a cardiac-based phenotypic shift in the SHR model and provide important insights into the beneficial function of concentric hypertrophy in hypertension-induced HF.

Dynamic weight-bearing test during jumping: A sensitive outcome measure of chronic osteoarthritis pain in rats

Pain due to osteoarthritis (OA) often occurs during locomotion in the vertical direction when joints are subjected to high mechanical load, e.g. during standing up from a chair or using stairs. To investigate joint pain in OA rat models, dynamic weight-bearing or gait analysis is traditionally conducted during horizontal walking on a flat surface. However, in chronic models of OA, which are of particular translational relevance for the disease, differences in the readouts between OA and control rats are often weak and of high variability leading to an insufficient assay window for drug profiling. To measure pain-related symptoms more sensitively, we conducted a dynamic weight-bearing test in the moment of a strong voluntary mechanical load. For that, we permanently housed rats in a four-story rat colony cage (RCC) and determined hind paw forces during voluntary jumping from one level to the next. This outcome measure was named jump incapacitance. After inducing OA by destabilizing the medial meniscus (DMM), we found that during jumps the average ipsilateral over contralateral hind paw forces were significantly reduced compared with healthy controls (jump incapacitance) from early- (day 7) to late-stage disease (day 90). An intra-articular injection of Zilretta (triamcinolone acetonide extended-release injectable suspension) attenuated OA-induced jump incapacitance after 8 days compared with DMM rats receiving vehicle (p = 0.069). In contrast, a CatWalk test for gait disturbance failed to detect any significant alterations in the chronic course of the DMM model. In conclusion, the dynamic weight-bearing test during jumping represents a novel method to characterize joint pain symptoms even in a slowly progressive OA rat model. It is sensitive, observer independent, relates to clinically relevant endpoints and demonstrates backtranslation of a drug that is approved for the treatment of OA knee pain.

Increases in concentric hypertrophy are driven by natural selection in the Spontaneously Hypertensive Rat Colony

Background Heart failure (HF) is a global health concern that affects nearly 26 million people each year. The Spontaneously Hypertensive Rat (SHR) was established in 1963 and is the most commonly used rodent model for studying human HF. Unlike humans, the SHRs develop hypertension around their reproductive age (i.e., when animals are selected for breeding), providing the opportunity for natural selection towards adaptive traits for hypertension-induced heart failure. Therefore, the primary objective of this review was to evaluate whether SHRs have evolved over time to the cardiac sequelae of hypertension. We hypothesized that, while the severity of hypertension will remain stable within the SHR colony, the HF phenotype will become less pronounced with time as a result of compensatory changes to manage high blood pressure. Methods We performed a retrospective review evaluating several indices of cardiovascular health in the SHR over the past 60 years. For statistical analyses, studies that met the inclusion criteria were separated into 2 cohorts: Initial (mid-late 1900’s) and Current (early 2000’s -present) Colony SHRs. Wistar-Kyoto rats (i.e., normotensive rats used to establish the SHR line via selective breeding) were used as controls to normalize changes in technique and methods that have occurred over these decades. Results Systolic blood pressure did not differ between Initial and Current Colony SHRs, indicating that the severity of hypertension had remained stable within the SHR Colony over time. Current Colony SHRs presented with increased cardiac concentric hypertrophy (i.e., elevated heart weight and posterior wall thickness). Since these changes were not observed in the Wistar-Kyoto control rats, cardiac-derived changes in Current Colony SHRs were unlikely due to differences in techniques, equipment, anesthesia or environmental conditions. Conclusion These findings establish that the SHR colony has evolved over time, with greater concentric hypertrophy. Using natural selection to find positive adaptive traits may be advantageous in identifying new therapeutic treatment strategies.

Repeated victorious and defeat experiences induce similar apical dendritic spine remodeling in CA1 hippocampus of rats

In this study, apical dendritic spine density of neurons in hippocampal, amygdalar and prefrontal cortical areas was compared in rats that were repeatedly winning or losing social conflicts. Territorial male wild-type Groningen (WTG) rats were allowed multiple daily attacks (>20 times) on intruder males in the resident-intruder paradigm. Frequent winning experiences are known to facilitate uncontrolled aggressive behavior reflected in aggressive attacks on anesthetized males which was also observed in the winners in this study. Both winners and losers were socially housed during the experiments; winners with females to stimulate territorial behavior, and losers with two other losing male rats. Twenty-four hours after the last social encounter, brains from experienced residential winners and repeatedly defeated intruder rats were collected and neuronal morphology in selected brain regions was studied via Golgi-Cox staining. Results indicate that spine density in the apical dendrites of the hippocampal CA1 reduced similarly in both winners and losers. In addition, winners showed increased spine densities at the proximal segments (20−30 μm) of the basolateral amygdala neurons and losers tended to show a decreased spine density at the more proximal segments of the infralimbic region of prefrontal cortex neurons. No effect of winning and losing was observed in the medial amygdala. The atrophic effect of repeated defeats in hippocampal and prefrontal regions was anticipated despite the fact that social housing of the repeatedly losing intruder males may have played a protective role. The reduction of hippocampal spine density in the winners seems surprising but supports previous findings in hierarchical dominant males in rat colonies. The dominants showed even greater shrinkage of the apical dendritic arbors of hippocampal CA3 pyramidal neurons compared to the stressed subordinates.