SV40 lymphomagenesis in Syrian golden hamsters

Simian virus 40 (SV40) isolates differ in oncogenic potential in Syrian golden hamsters following intraperitoneal inoculation. Here we describe the effect of intravenous exposure on tumor induction by SV40. Strains SVCPC (simple regulatory region) and VA45-54(2E) (complex regulatory region) were highly oncogenic following intravenous inoculation, producing a spectrum of tumor types. Three lymphoma cell lines were established; all expressed SV40 T-antigen, were immortalized for growth in culture, and were tumorigenic following transplantation in vivo. New monoclonal antibodies directed against hamster lymphocyte surface antigens are described. The cell lines expressed MHC class II and macrophage markers and were highly phagocytic, indicating a histiocytic origin. Many hamsters that remained tumor-free developed SV40 T-antigen antibodies, suggesting that viral replication occurred. This study shows that route of exposure influences the pathogenesis of SV40-mediated carcinogenesis, that SV40 strain VA45-54(2E) is lymphomagenic in hamsters, that hamster lymphoid cells of histiocytic origin can be transformed in vivo and established in culture, and that reagents to hamster leukocyte differentiation molecules are now available.     

Metabolic effects of voluntary wheel running in young and old Syrian golden hamsters

To explore the metabolic effects of high volume wheel running in the Syrian golden hamster, 6-week old (YOUNG) and 6-month old (OLD) male animals were randomly divided into sedentary (i.e., YOUNG-S or OLD-S) or running wheel (i.e., YOUNG-RW or OLD-RW) groups (n = 8/group). RW groups had 24-h access to activity wheels while S were housed in standard rodent cages. At the start of wheel exposure, the number of revolutions were similar in both groups, but by day 15 were nearly two-fold higher in the YOUNG vs. OLD. OLD ate more than YOUNG and wheel running increased food intake by approximately 50%. YOUNG-RW maintained the same total body mass as YOUNG-S, while OLD-RW had a transient weight loss of approximately 10 g. Perirenal fat mass was smaller in YOUNG- and OLD-RW groups compared with S groups (45% and 66%, respectively. Plantaris muscle cytochrome c oxidase activity was also approximately 2-fold higher in YOUNG-RW than in YOUNG-S hamsters but was similar between OLD-RW and OLD-S groups. Plasma leptin levels were approximately 60% lower in YOUNG-RW compared with YOUNG-S and correlated significantly with visceral fat pad mass (r2 = 0.58, p = 0.001). Corticosterone levels were lower in YOUNG-RW (13.0 +/- 0.36 ng/ml) than in YOUNG-S (16.4 +/- 0.83 ng/ml) hamsters and higher in OLD-RW (22.62 +/- 0.47 ng/ml) than in OLD-S (15.54 +/- 0.13 ng/ml) hamsters. These observations reveal that the hamster is a suitable model for accelerating the effects of exercise on body composition and metabolic alterations associated with training and that the training adaptations are more pronounced in younger compared with older hamsters, possibly as a result of the higher voluntary wheel activity in the former group.     

Changes in glycoconjugates revealed by lectin staining in the developing airways of Syrian golden hamsters

Lectin binding was studied in the developing airways of Syrian golden hamsters on gestational days 11–16 (day 16 is the day of birth). The trachea and lungs were fixed in 4% formaldehyde-1% glutaraldehyde, 6% mercuric chloride-1% sodium acetate-0.1% glutaraldehyde, and 95% ethanol; embedded in paraffin; and stained with eight lectin-horseradish peroxidase conjugates: Triticum vulgare (WGA), Dolichos biflorus (DBA), Helix pomatia (HPA), Maclura pomifera (MPA), Griffonia simplicifolia I-B4 (GSA I-B4), Arachis hypogaea (PNA), Ulex europeus I (UEA I), and Limulus polyphemus (LPA). Each lectin yielded a characteristic staining pattern, which modulated throughout development. In general, changes in staining characteristics of the tracheal epithelium preceded similar changes in the lobar bronchus, bronchiole, and alveolus. In the case of UEA I, MPA, WGA, and HPA, staining increased with time uniformly over the luminal surface of all epithelial cells. However, in the case of PNA, GSA I-B4, and LPA, after the differentiation of ciliated and secretory cells, the apical surfaces of the ciliated cells stained more intensely than the apical surfaces of the secretory cells. Neuraminidase pretreatment enhanced PNA and GSA I-B4 staining in both cell types. In the case of PNA, these light microscopic observations were confirmed by ultrastructural study. Unlike the other lectins, the pattern of staining with DBA was unusual. Staining was moderate at first, then decreased (days 13 and 14), then increased at all airway levels. This study shows that different glycoconjugates modulate in airway epithelial cells throughout fetal development.     

Changes in glycoconjugates revealed by lectin staining in the developing airways of Syrian golden hamsters.

Lectin binding was studied in the developing airways of Syrian golden hamsters on gestational days 11-16 (day 16 is the day of birth). The trachea and lungs were fixed in 4% formaldehyde-1% glutaraldehyde, 6% mercuric chloride-1% sodium acetate-0.1% glutaraldehyde, and 95% ethanol; embedded in paraffin; and stained with eight lectin-horseradish peroxidase conjugates: Triticum vulgare (WGA), Dolichos biflorus (DBA), Helix pomatia (HPA), Maclura pomifera (MPA), Griffonia simplicifolia I-B4 (GSA I-B4), Arachis hypogaea (PNA), Ulex europeus I (UEA I), and Limulus polyphemus (LPA). Each lectin yielded a characteristic staining pattern, which modulated throughout development. In general, changes in staining characteristics of the tracheal epithelium preceded similar changes in the lobar bronchus, bronchiole, and alveolus. In the case of UEA I, MPA, WGA, and HPA, staining increased with time uniformly over the luminal surface of all epithelial cells. However, in the case of PNA, GSA I-B4, and LPA, after the differentiation of ciliated and secretory cells, the apical surfaces of the ciliated cells stained more intensely than the apical surfaces of the secretory cells. Neuraminidase pretreatment enhanced PNA and GSA I-B4 staining in both cell types. In the case of PNA, these light microscopic observations were confirmed by ultrastructural study. Unlike the other lectins, the pattern of staining with DBA was unusual. Staining was moderate at first, then decreased (days 13 and 14), then increased at all airway levels. This study shows that different glycoconjugates modulate in airway epithelial cells throughout fetal development.     

Role of caloric homeostasis and reward in alcohol intake in Syrian golden hamsters

The Syrian golden hamster drinks alcohol readily, but only achieves moderate blood alcohol levels, and does not go through withdrawal from alcohol. Because the hamster is a model of caloric homeostasis, both caloric content and reward value may contribute to the hamster's alcohol consumption. The current study examines alcohol consumption in the hamster when a caloric or non-caloric sweet solution is concurrently available and caloric intake in the hamster before, during, and after exposure to either: alcohol, sucrose or saccharin. In Experiments 1 and 2, hamsters were given access to alcohol (15% v/v) and water; once alcohol consumption steadied, a bottle containing an ascending concentration of sucrose (99-614 mM) or saccharin (2-10 mM), or water was added. In Experiment 3, hamsters were given access to alcohol (15% v/v), sucrose (614 mM), saccharin (4 mM), or a second water bottle for 14 days. After the second bottle was removed, measurements continued for 14 days. Sucrose exposure suppressed alcohol consumption at concentrations lower in calories than the alcohol solution. Saccharin exposure failed to suppress alcohol consumption. Exposure to sucrose and alcohol but not saccharin decreased food intake. Decreased alcohol consumption in response to a caloric sweetener and decreased food intake during alcohol exposure support that alcohol consumption by the hamster is mediated by caloric content. However, suppression of alcohol intake by a sucrose solution of lower caloric content and the equivalent intake of individual alcohol, sucrose and saccharin solutions support a role for reward value in alcohol consumption.     

Lectin histochemistry of developing submandibular glands of fetal Syrian golden hamsters

Summary Lectin binding was studied in the developing submandibular glands of fetal Syrian golden hamsters (Mesocricetus auratus) from gestational day 12 to 16 (the day of birth). The fetuses were fixed, embedded in paraffin, sectioned and stained with nine lectin-horseradish peroxidase conjugates: concanavalin A (Con A), wheat germ agglutinin (WGA), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Maclura pomifera agglutinin (MPA), Griffonia simplicifolia agglutinin I-B₄ (GSA I-B4), peanut agglutinin (PNA), Ulex europens agglutinin I (UEA I) and Limulus polyphemus agglutinin (LPA). The developing glands showed dramatic morphological alterations on a daily basis, accompanied by progressive changes in lectin staining. On day 12 the primitive gland showed only trace lectin staining with WGA, HPA, MPA, PNA and UEA I, but by day 13, strong staining with these lectins, as well as with DBA, was seen at the ductal lumenal surface, after the formation of the ductal lumens. Secretory granules first appeared in cells of the primitive acini on day 14; the secretion products were stained strongly with WGA, DBA, HPA, MPA, PNA and UEA I. On day 15, the secretion products were also stained moderately with GSA I-B4. Secretory differentiation was further developed on day 16, but the staining intensity of the mucins with the different lectins varied among the secretory cells. LPA failed to stain any part of the gland throughout the observation period, and Con A stained only glycogen.This work was supported by National Institutes of Health Grant HL37640.     

Inhibition of severe acute respiratory syndrome-associated coronavirus infection by equine neutralizing antibody in golden Syrian hamsters

Equine anti-severe acute respiratory syndrome-associated coronavirus F(ab')(2) has been verified to protect mice from infection with severe acute respiratory syndrome-associated coronavirus (SARS-CoV). However, before potential clinical application, the antibody needs to be tested in as many animal models as possible to ensure its safety and efficiency. In this study, after verification by various methods that the golden Syrian hamster constitutes a model susceptible to SARS-CoV infection, we confirmed that the antibody could protect animals completely from SARS-CoV infection in the preventive setting. More importantly, the antibody could reduce viral titers or copies by approximately 10(3)- to 10(4)-fold in animal lung after virus exposure, compared with negative control. These data provide further evidence to warrant clinical studies of this antibody in the treatment and prevention of SARS.     

Development of the conducting airway epithelium in fetal Syrian golden hamsters during normal and diabetic pregnancies

The conducting airway epithelium of fetal Syrian golden hamsters was studied from gestational day 12 to day 15, during normal and uncontrolled diabetic pregnancies. Diabetes was induced in the pregnant hamsters by injecting streptozotocin at 60 mg/kg body weight, subcutaneously, early on gestational day 10. Cells in S-phase were labelled immunochemically with bromodeoxyuridine (BrdU), and the day on which endocrine cells and ciliated cells first appeared was determined. In control fetuses, the BrdU-labelling indices (LI's) of different anatomical airway levels were significantly different from one gestational day to the next. For example, the LI of the lobar bronchus was significantly different on each gestational day (P less than .0001), and the same was true of the bronchioles. Moreover, the difference between LI's of the lobar bronchus and bronchioles-terminal buds was highly significant on day 12 (P less than .0001), and on day 13 the differences between lobar bronchus and bronchioles, lobar bronchus and terminal buds, and bronchioles and terminal buds were also highly significant (P less than .0001). However, on gestational days 14 and 15, the LI's were reduced and were comparable at different airway levels. The BrdU-labelling indices were very consistent among fetuses of the same age, and the differences between the average LI's for pups of different litters was numerically very small. Hyperglycemia (mild, moderate, severe) did not alter LI's in the fetal airway epithelial cells. Furthermore, although glycogen was not depleted from the airway epithelium of the hyperglycemic fetuses as it was in the controls, the endocrine cells first appeared on gestational days 12, 13, and 14, respectively, in the trachea, lobar bronchus and bronchioles, followed 1 day later by the ciliated cells, in the fetuses of control and diabetic mothers. In our experimental model, induction of diabetes in the pregnant hamsters on gestational day 10 did not appear to alter development or differentiation of the fetal conducting airway epithelium.     

Development of the conducting airway epithelium in fetal Syrian golden hamsters during normal and diabetic pregancies

The conducting airway epithelium of fetal Syrian golden hamsters was studied from gestational day 12 to day 15, during normal and uncontrolled diabetic pregnancies. Diabetes was induced in the pregnant hamsters by injecting streptozotocin at 60 mg/kg body weight, subcutaneously, early on gestational day 10. Cells in S-phase were labelled immunochemically with bromodeoxyuridine (BrdU), and the day on which endocrine cells and ciliated cells first appeared was determined. In control fetuses, the BrdU-labelling indices (LI's) of different anatomical airway levels were significantly different from one gestational day to the next. For example, the LI of the lobar bronchus was significantly different on each gestational day (P.0001), and the same was true of the bronchioles. Moreover, the difference between LI's of the lobar bronchus and bronchioles-terminal buds was highly significant on day 12 (P <.0001), and on day 13 the differences between lobar bronchus and bronchioles, lobar bronchus and terminal buds, and bronchioles and terminal buds were also highly significant (P .0001). However, on gestational days 14 and 15, the LI's were reduced and were comparable at different airway levels. The BrdU-labelling indices were very consistent among fetuses of the same age, and the differences between the average LI's for pups of different litters was numerically very small. Hyperglycemia (mild, moderate, severe) did not alter LI's in the fetal airway epithelial cells. Furthermore, although glycogen was not depleted from the airway epithelium of the hyperglycemic fetuses as it was in the controls, the endocrine cells first appeared on gestational days 12, 13, and 14, respectively, in the trachea, lobar bronchus and bronchioles, followed 1 day later by the ciliated cells, in the fetuses of control and diabetic mothers. In our experimental model, induction of diabetes in the pregnant hamsters on gestational day 10 did not appear to alter development or diferentiation of the fetal conducting airway epithelium.     

Development of intrapancreatic transplantable model of pancreatic duct adenocarcinoma in Syrian golden hamsters.

Intrapancreatic and subcutaneous (SC) inoculation of cultured pancreatic cancer cells, derived from an induced primary pancreatic cancer in a Syrian hamster, resulted in tumor take in all recipient hamsters. The intrapancreatic allografts grew rapidly, were invasive, and metastasized into the lymph nodes and liver in 2 of 9 cases. In comparison, SC tumors grew relatively slower and formed a large encapsulated mass without invasion and metastases. Histologically, tumors of both sites showed fairly well-differentiated adenocarcinomas of ductal/ductular type resembling the induced primary cancer. Similar to the primary induced pancreatic cancers, tumor cells of both allografts expressed blood-group-related antigens, including A, B, H, Le(b), Le(y), Le(x), and tumor-associated antigen TAG-72. The tumor cells did not express Le(a), CA 19-9, 17-1A, or DU-PAN-2. The expression of these antigens was retained in the metastases and presented the same patterns of reactivity as the allografts. Thus intrapancreatic transplantation provides a rapid model for production of pancreatic cancer with morphologic similarities to human pancreatic cancer.     

Establishment of a transplantable carcinoma arising from the intrahepatic bile duct in Syrian golden hamsters

A subcutaneously transplantable cancer line from the intrahepatic bile duct (IHBD) induced byN- nitrosobis(2-oxopropyl) amine was established in Syrian golden hamsters. The doubling time of this tumour was 2.6 days when 2x10⁵ tumour cells were inoculated subcutaneously (take-up rate was 100%). Growth of the tumour was significantly faster in male hamsters but neither oestrogen nor androgen receptors were detected in the tumour. The primary and all allograft tumours were tubular adenocarcinomas with fibrosis and a scirrhous pattern resembling human IHBD carcinoma of the peripheral type. Transmission electron microscopic findings showed irregular glands covered with numerous microvilli. Blood-group-related antigens including A, B and H were positive. P-Glycoprotein, which is an indicator of multidrug resistance, was also positive. Carcinoembryonic antigen and CA19-9 as general tumour markers of the biliary tract were negative. The deoxyribonucleic acid (DNA) pattern of this transplantable carcinoma was diploid. This newly established animal model of a transplantable IHBD carcinoma can be used to examine the mechanisms of synthesis and secretion of tumour-associated antigens and to study potential therapeutic agents.     

Pathogenesis of a phleboviral infection (Punta Toro virus) in golden Syrian hamsters

Summary The hamster,Mesocricetus auratus, was examined as a possible model for investigating the poorly defined pathogenesis of the familyBunyaviridae, genusPhlebovirus. Punta Toro virus (PTV) isolates from Eastern Panama were highly virulent for two outbred and five inbred hamster strains, while isolates from western Panama were of low virulence. The Adames strain (eastern Panama) of PTV (LD₅₀ approximately 1 PFU, sc) caused an acute fatal disease (average survival time, 3.8 days) in 10-week-old Lak: LVG (SYR) hamsters. Severe necrosis of the liver, spleen, and small intestine was associated with extensive expression of viral antigen in these organs. The Balliet strain (western Panama) of PTV (LD₅₀>6log₁₀ PFU, subcutaneously) caused a mild hepatocellular infection with peak viral liver titers of 3–4 log₁₀ PFU/g compared to 8–9 log₁₀ PFU/g for the Adames strain. We observed histological lesions in the red pulp of the spleen or the lamina propria of the small intestine with the Adames strain. Lesions in the hamsters had characteristics of disseminated intravascular coagulation (DIC). The PTV-hamster model shares similarities to Rift Valley fever (phleboviral disease), which causes fatal disease in man and domesticated ruminants.     

Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis.

N-nitrosomorpholine (NM)-induced pulmonary carcinogenesis was examined by light and electron microscopy in a 20-week serial sacrifice study using Syrian golden hamsters. First to be observed were a proliferation of endocrine APUD cells and a formation of lamellated inclusion bodies in the cytoplasm of Clara cells. After continued NM treatment, APUD cells underwent squamous metaplasia and Clara cells invaded the pulmonary tissues adjacent to the bronchi. Lung tumors consisted of cells possessing numerous lamellated inclusion bodies in their cytoplasm and a few squamous metaplastic and APUD cells. The observed pathologic alterations closely resembled those found after treatment with N-diethylnitrosamine (DEN) and N-dibutylnitrosamine (DBN) but were completely different from the cellular reactions induced by polycyclic aromatic hydrocarbons. It is concluded that the observed alterations of APUD cells and Clara cells are specific to nitrosamines.     

Yellow fever virus infection in Syrian golden hamsters: relationship between cytokine expression and pathologic changes

Infection of primates by yellow fever virus (YFV) often results in severe multi-organ failure with marked histologic abnormalities. However, the role of host's immune response, particularly innate immunity, in disease process is unclear. In this study, we used a well established hamster model of yellow fever to examine the dynamic changes of cytokine expression and histopathology in the liver, spleen, kidney, and heart during the course of YFV infection. We observed that the levels of inflammatory cytokines (IFN-gamma, IL-2, TNF-alpha) in the liver were significantly reduced in the mid-stage of infection (8 days), but were elevated later (12 days). In contrast, IL-12p40 was elevated throughout the infection. The levels of IFN-gamma, IL-2, and TNF-alpha were increased in the spleen, kidney, and heart throughout the study period. For regulatory cytokines, IL-10 was significantly increased, and TGF-beta was reduced in the liver, spleen and heart in both early and mid-stages of infection, but was elevated in the kidney during the entire course of infection. In view of the pathologic changes, the observed cytokine profiles suggest that YFV has immunosuppressive effects, which contribute to liver damage in the mid-stage of infection, followed by an immunopathogenic mechanism that leads to disease progression during the late-stages of infection. Our findings support the hypothesis that organ injury by YFV is probably due to a combination of multiple factors, including direct viral injury and host innate immune responses.     

Pancreatic neoplasms induced in Syrian golden hamsters. I. Scanning electron microscopic observations.

Pancreases from Syrian golden hamsters treated with N-nitrosobis(2-hydroxy-proply)amine for 10 to 25 weeks were examined under scanning electron microscopy (SEM). Findings indicate that the neoplasms originated from the ductal epithelium and developed progressively. Adenomas were lined by epithelium of differing cells types, ranging from a flat singly ciliated form to cuboidal-columnar types, or to mixed cell populations. The epithelial lining of the ductal carcinomas exhibited tubular and papillary cystic spaces, and cell surfaces were similar to the cuboidal and columnar epithelium of adenomas and of ductal epithelial hyperplasia. However, microvilli were dense and of varied lengths. The SEM observations correlated with patterns seen in routine histologic preparations.     

Short photoperiod effects on kidney growth in male Syrian hamsters

The transfer of Syrian golden hamsters from a long to a short photoperiod (SP) leads to reduced circulating levels of several anterior pituitary hormones including thyrotropin stimulating hormone (TSH), luetinizing hormone (LH) and follicle stimulating hormone (FSH), while growth hormone (GH) is unaffected. These hormonal changes are associated with accelerated rates of body weight gain and gonadal atrophy in this species, but the effects on growth of other organs, specifically the kidney, are unknown. In this study, the effect of SP treatment on kidney and body weights of intact and uninephrectomized male Syrian golden hamsters was evaluated. Seventy-two young adult male hamsters were acclimatized to long photoperiod (LP) consisting of a light/dark schedule of 14/10 hours (LD 14:10). Two weeks later one half of the animals were transferred to SP (LD 10:14) Subgroups of six hamsters underwent either left nephrectomy or sham left nephrectomy two, five and eight weeks after transfer to SP and were sacrificed two weeks after surgery. The relative kidney weights (kidney weights/100 g body weight) of the sham operated animals were significantly reduced after seven and ten weeks of SP treatment (p less than 0.01). Absolute kidney weights were depressed after eight (p less than 0.05) and ten weeks in SP. The percentage increase in the weight of the hypertrophied kidney following uninephrectomy was unaffected by SP. Differences in body weights were due to increased fat in SP-treated hamsters; nonetheless, the logs of kidney and body weights were highly correlated in both LP (r = 0.73) and SP (r = 0.78). Lean body weights, determined by body compositional analysis, were less well correlated with kidney weights in LP (r = 0.53) and unrelated in SP (r = 0.16). The mechanism retarding kidney growth was not elucidated, but may include SP-induced changes in TSH, LH, or a specific LH-like pituitary renotropin proposed by Nomura et al. (1982). The observation that compensatory renal growth proceeds despite inhibition of kidney growth in intact animals suggests that separate mechanisms regulate these processes.     

Immunohistochemical demonstration of Clara cell antigen in lung tumors of bronchiolar origin induced by N-nitrosodiethylamine in Syrian golden hamsters.

Both alveolar type II cells and Clara cells have been suggested as cells of origin of human bronchioloalveolar lung carcinomas and other pulmonary neoplasms, based on the presence of cell specific markers identified by immunocytochemical methods. Alveolar type II cell origin of solid and papillary lung tumors of the mouse has been demonstrated, and Clara cells have been suggested as cell of origin for hamster pulmonary neoplasms. Therefore, chemically induced bronchiolar hyperplasias and pulmonary neoplasms of Syrian golden hamsters were analyzed by avidin-biotin immunohistochemistry to localize a hamster-specific Clara cell antigen (CCA) and keratin. The hamsters had been treated subcutaneously with multiple doses of N-nitrosodiethylamine (NDEA). Proliferative lesions of low cuboidal, tall columnar, or pleomorphic cells were present within bronchioles or adjacent to airways in the alveolar parenchyma. Frequently areas of squamous cell differentiation were present focally or diffusely that were immunoreactive for cytokeratin. Immunoreactivity for cytokeratin was also noted for hyperplastic bronchiolar neuroepithelial bodies. Cellular hyperplasias extending out into the alveolar parenchyma contained ciliated cells and frequently consisted of cells immunoreactive for CCA, showing them to be of bronchiolar Clara cell origin. Tumors developed from bronchiolar cell hyperplasias localized within bronchioles and from bronchiolar cells lining former alveolar walls. Neoplastic growth patterns were tubulo-papillary, forming loose networks or densely cellular areas. Immunoreactivity for cytoplasmic CCA was found in 50% of the tumors and was seen most frequently in small cuboidal cells and larger, vacuolated cells scattered throughout the neoplasms. In summary, evidence is presented that NDEA-induced pulmonary tumors of the Syrian golden hamster originated from cells lining bronchioles and from extrabronchiolar Clara cell hyperplasias of the terminal bronchioles. As the pulmonary tumors of the hamsters progressed towards a squamoid cell type, CCA was no longer detectable but cells became immunoreactive for keratin.     

Recognition of competitors by male golden hamsters

Golden hamsters, like many animals, form dominant/subordinate relationships after aggressive encounters. We examined whether behavioral responses by males that won or lost fights would differ toward familiar and unfamiliar male stimulus animals. In Experiment 1, male winners or losers of fights explored an arena containing a confined stimulus animal that was either familiar or novel and had either won or lost a fight. Compared to dominant males, losers spent less time in proximity to stimulus males and investigated them less. Losers also displayed higher levels of stretch-attend postures (indicative of risk assessment) than winners, and they showed more escape and locomotion in response to familiar winners than to unfamiliar winners, indicating recognition of the male that they had lost to. In Experiment 2, losers scent marked less to the odors of a familiar winner than to those of an unfamiliar winner. Thus, male hamsters appear to use familiarity with a former opponent's odors to adaptively regulate their responses to variations in social threat.