Dominant Hamsters Research Articles

Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex

Chronic stress increases activity of the brain’s innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability.

Activation of androgen receptor-expressing neurons in the posterior medial amygdala is associated with stress resistance in dominant male hamsters

Social stress is a negative emotional experience that can increase fear and anxiety. Dominance status can alter the way individuals react to and cope with stressful events. The underlying neurobiology of how social dominance produces stress resistance remains elusive, although experience-dependent changes in androgen receptor (AR) expression is thought to play an essential role. Using a Syrian hamster (Mesocricetus auratus) model, we investigated whether dominant individuals activate more AR-expressing neurons in the posterior dorsal and posterior ventral regions of the medial amygdala (MePD, MePV), and display less social anxiety-like behavior following social defeat stress compared to subordinate counterparts. We allowed male hamsters to form and maintain a dyadic dominance relationship for 12 days, exposed them to social defeat stress, and then tested their approach-avoidance behavior using a social avoidance test. During social defeat stress, dominant subjects showed a longer latency to submit and greater c-Fos expression in AR+ cells in the MePD/MePV compared to subordinates. We found that social defeat exposure reduced the amount of time animals spent interacting with a novel conspecific 24 h later, although there was no effect of dominance status. The amount of social vigilance shown by dominants during social avoidance testing was positively correlated with c-Fos expression in AR+ cells in the MePV. These findings indicate that dominant hamsters show greater neural activity in AR+ cells in the MePV during social defeat compared to their subordinate counterparts, and this pattern of neural activity correlates with their proactive coping response. Consistent with the central role of androgens in experience-dependent changes in aggression, activation of AR+ cells in the MePD/MePV contributes to experience-dependent changes in stress-related behavior.

Activity of a vmPFC-DRN Pathway Corresponds With Resistance to Acute Social Defeat Stress.

The ventromedial prefrontal cortex (vmPFC) plays a critical role in stress resilience through top-down inhibition of key stress-sensitive limbic and hindbrain structures, including the dorsal raphe nucleus (DRN). In a model of experience-dependent stress resistance, socially dominant Syrian hamsters display fewer signs of anxiety following acute social defeat when compared to subordinate or control counterparts. Further, dominants activate vmPFC neurons to a greater degree during stress than do subordinates and become stress-vulnerable following pharmacological inhibition of the vmPFC. Dominants also display fewer stress-activated DRN neurons than subordinates do, suggesting that dominance experience gates activation of vmPFC neurons that inhibit the DRN during social defeat stress. To test whether social dominance alters stress-induced activity of a vmPFC-DRN pathway, we injected a retrograde tracer, cholera toxin B (CTB), into the DRN of dominant, subordinate, and control hamsters and used a dual-label immunohistochemical approach to identify vmPFC neurons co-labeled with CTB and the defeat-induced expression of an immediate early gene, cFos. Results indicate that dominant hamsters display more cFos+ and dual-labeled cells in layers V/VI of infralimbic and prelimbic subregions of the vmPFC compared to other animals. Furthermore, vmPFC-DRN activation corresponded directly with proactive behavioral strategies during defeat, which is indicative of stress resilience. Together, results suggest that recruiting the vmPFC-DRN pathway during acute stress corresponds with resistance to the effects of social defeat in dominant hamsters. Overall, these findings indicate that a monosynaptic vmPFC-DRN pathway can be engaged in an experience-dependent manner, which has implications for behavioral interventions aimed at alleviating stress-related psychopathologies.

Social Dominance Modulates Stress-induced Neural Activity in Medial Prefrontal Cortex Projections to the Basolateral Amygdala

Stress is a contributing factor in the etiology of several mood and anxiety disorders, and social defeat models are used to investigate the biological basis of stress-related psychopathologies. Male Syrian hamsters are highly aggressive and territorial, but after social defeat they exhibit a conditioned defeat (CD) response which is characterized by increased submissive behavior and a failure to defend their home territory against a smaller, non-aggressive intruder. Hamsters with dominant social status show increased c-Fos expression in the infralimbic (IL) cortex following social defeat and display a reduced CD response at testing compared to subordinates and controls. In this study, we tested the prediction that dominants would show increased defeat-induced neural activity in IL, but not prelimbic (PL) or ventral hippocampus (vHPC), neurons that send efferent projections to the basolateral amygdala (BLA) compared to subordinates. We performed dual immunohistochemistry for c-Fos and cholera toxin B (CTB) and found that dominants display a significantly greater proportion of double-labeled c-Fos + CTB cells in both the IL and PL. Furthermore, dominants display more c-Fos-positive cells in both the IL and PL, but not vHPC, compared to subordinates. These findings suggest that dominant hamsters selectively activate IL and PL, but not vHPC, projections to the amygdala during social defeat, which may be responsible for their reduced CD response. This project extends our understanding of the neural circuits underlying resistance to social stress, which is an important step toward delineating a circuit-based approach for the prevention and treatment of stress-related psychopathologies.

Dominance relationships in Syrian hamsters modulate neuroendocrine and behavioral responses to social stress

Stress is a well-known risk factor for psychopathology and rodent models of social defeat have strong face, etiological, construct and predictive validity for these conditions. Syrian hamsters are highly aggressive and territorial, but after an acute social defeat experience they become submissive and no longer defend their home territory, even from a smaller, non-aggressive intruder. This defeat-induced change in social behavior is called conditioned defeat (CD). We have shown that dominant hamsters show increased neural activity in the ventromedial prefrontal cortex (vmPFC) following social defeat stress and exhibit a reduced CD response at social interaction testing compared to subordinates. Although the vmPFC can inhibit the neuroendocrine stress response, it is unknown whether dominants and subordinates differ in stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that, following acute social defeat, dominants exhibit decreased submissive and defensive behavior compared to subordinates but do not differ from subordinates or social status controls (SSCs) in defeat-induced cortisol concentrations. Furthermore, both dominants and SSCs show greater corticotropin-releasing hormone (CRH) mRNA expression in the basolateral/central amygdala compared to subordinates, while there was no effect of social status on CRH mRNA expression in the paraventricular nucleus of the hypothalamus or bed nucleus of the stria terminalis. Overall, status-dependent differences in the CD response do not appear linked to changes in stress-induced cortisol concentrations or CRH gene expression, which is consistent with the view that stress resilience is not a lack of a physiological stress response but the addition of stress coping mechanisms.Lay summaryDominant hamsters show resistance to the behavioral effects of acute social defeat compared to subordinates, but it is unclear whether social status modulates the neuroendocrine stress response in Syrian hamsters. This study indicates that dominant social status does not alter stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis, which suggests that the ability of dominants to cope with social defeat stress is not associated with changes in their neuroendocrine stress response.

Individual recognition of social rank and social memory performance depends on a functional circadian system

In a natural environment, social abilities of an animal are important for its survival. Particularly, it must recognize its own social rank and the social rank of a conspecific and have a good social memory. While the role of the circadian system for object and spatial recognition and memory is well known, the impact of the social rank and circadian disruptions on social recognition and memory were not investigated so far. In the present study, individual recognition of social rank and social memory performance of Djungarian hamsters revealing different circadian phenotypes were investigated. Wild type (WT) animals show a clear and well-synchronized daily activity rhythm, whereas in arrhythmic (AR) hamsters, the suprachiasmatic nuclei (SCN) do not generate a circadian signal. The aim of the study was to investigate putative consequences of these deteriorations in the circadian system for animalś cognitive abilities.Hamsters were bred and kept under standardized housing conditions with food and water ad libitum and a 14l/10 D lighting regimen. Experimental animals were assigned to different groups (WT and AR) according to their activity pattern obtained by means of infrared motion sensors. Before the experiments, the animals were given to develop a dominant-subordinate relationship in a dyadic encounter. Experiment 1 dealt with individual recognition of social rank. Subordinate and dominant hamsters were tested in an open arena for their behavioral responses towards a familiar (known from the agonistic encounters) or an unfamiliar hamster (from another agonistic encounter) which had the same or an opposite social rank. The investigation time depended on the social rank of the WT subject hamster and its familiarity with the stimulus animal. Both subordinate and dominant WT hamsters preferred an unfamiliar subordinate stimulus animal. In contrast, neither subordinate nor dominant AR hamsters preferred any of the stimulus animals. Thus, disruptions in circadian system result in an impaired individual recognition of social rank.A social recognition/discrimination task was used in Experiment 2 to quantify social memory performance. In a training session, the hamsters were confronted with two unfamiliar stimulus animals. In the test session, one of the two animals was replaced. The training-test interval was 2min or 24h. The times animals did explore the novel and the familiar stimulus animal were recorded, and the discrimination index as a measure of cognitive performance was calculated. Behavioral tests revealed that after 2min both subordinate and dominant WT hamsters were able to discriminate between familiar and novel stimulus animals but after 24h only the subordinate animals. On contrary in AR hamsters, only subordinates were able to perform the social recognition/discrimination task and only after a training-test interval of 2min.The results show that the social rank and the circadian system have an impact on the cognitive abilities of Djungarian hamsters. Disruptions of circadian rhythms impair individual recognition and social memory performance.

Winning agonistic encounters increases testosterone and androgen receptor expression in Syrian hamsters

Winning aggressive disputes is one of several experiences that can alter responses to future stressful events. We have previously tested dominant and subordinate male Syrian hamsters in a conditioned defeat model and found that dominant individuals show less change in behavior following social defeat stress compared to subordinates and controls, indicating a reduced conditioned defeat response. Resistance to the effects of social defeat in dominants is experience-dependent and requires the maintenance of dominance relationships for 14days. For this study we investigated whether winning aggressive interactions increases plasma testosterone and whether repeatedly winning increases androgen receptor expression. First, male hamsters were paired in daily 10-min aggressive encounters and blood samples were collected immediately before and 15min and 30min after the formation of dominance relationships. Dominants showed an increase in plasma testosterone at 15min post-interaction compared to their pre-interaction baseline, whereas subordinates and controls showed no change in plasma testosterone. Secondly, we investigated whether 14days of dominant social status increased androgen or estrogen alpha-receptor immunoreactivity in brain regions that regulate the conditioned defeat response. Dominants showed more androgen, but not estrogen alpha, receptor immuno-positive cells in the dorsal medial amygdala (dMeA) and ventral lateral septum (vLS) compared to subordinates and controls. Finally, we showed that one day of dominant social status was insufficient to increase androgen receptor immunoreactivity compared to subordinates. These results suggest that elevated testosterone signaling at androgen receptors in the dMeA and vLS might contribute to the reduced conditioned defeat response exhibited by dominant hamsters.

A low-cost automated apparatus for investigating the effects of social defeat in Syrian hamsters

We describe an automated apparatus that can be used to investigate the effects of defeat in hamsters. It consists of a covered alleyway that leads to a box, or arena, where hamsters can be kept separate or allowed to fight. The alleyway is divided into seven equal-sized chambers. Low-power lasers and laser detectors are used to keep track of a hamster's position in the alleyway. A CFL flood lamp placed over the chamber farthest from the arena generates a light gradient in the alleyway that engenders in the subjects a preference for the darker chambers near the arena. A computer automatically records the interruption of the laser beams and yields three measures: average position, the frequency of visits to each chamber, and the frequency of changes in direction of travel in each chamber. The results of a pilot study indicated that when a dominant hamster was placed behind a screened gate in the arena and a subordinate hamster was placed in the alleyway, the subordinate maintained a significantly greater distance from the dominant than did a nondefeated hamster. The subordinate hamster also changed its direction of travel more frequently than did the nondefeated hamster. The results suggest that conditioned fear was elicited in the defeated hamster by proximity to the dominant hamster, an effect that is consistent with published results in which the data were recorded manually or by using commercially available event-tracking software.

Social defeat and footshock increase body mass and adiposity in male Syrian hamsters

Obesity is a world-wide epidemic, and many factors, including stress, have been linked to this growing trend. After social stress (i.e., defeat), subordinate laboratory rats and most laboratory mice become hypophagic and, subsequently, lose body mass; the opposite is true of subordinate Syrian hamsters. After social defeat, Syrian hamsters become hyperphagic and gain body mass compared with nonstressed controls. It is unknown whether this increase in body mass and food intake is limited to subordinate hamsters. In experiment 1, we asked, do dominant hamsters increase food intake, body mass, and adiposity after an agonistic encounter? Subordinate hamsters increased food intake and body mass compared with nonstressed controls. Although there was no difference in food intake or absolute body mass between dominant and nonstressed control animals, cumulative body mass gain was significantly higher in dominant than in nonstressed control animals. Total carcass lipid and white adipose tissue (WAT) (i.e., retroperitoneal and epididymal WAT) masses were significantly increased in subordinate, but not dominant, hamsters compared with nonstressed controls. In experiment 2, we asked, does footshock stress increase food intake, body mass, and adiposity. Hamsters exposed to defeat, but not footshock stress, increased food intake relative to nonstressed controls. In animals exposed to defeat or footshock stress, body mass, as well as mesenteric WAT mass, increased compared with nonstressed controls. Collectively, these data demonstrate that social and nonsocial stressors increase body and lipid mass in male hamsters, suggesting that this species may prove useful for studying the physiology of stress-induced obesity in some humans.

Using an animal model to assess the long-term behavioral and biological consequences of adolescent abuse and exposure to alcohol.

During adolescence or adulthood, male hamster siblings were divided into control and experimental groups and exposed to periods of either mild or traumatic stress outside their individual nests. Mild stress is the simple exposure to a novel environment while the traumatic stressor is repeated daily subjugation by a dominant hamster. Over adolescence and adulthood, animals had free access to alcohol. The behavior and neuroendocrinology were assessed over these developmental periods in response to these environmental conditions. As adults, animals with a history of traumatic stress in adolescence showed inappropriate and excessive aggressive behavior. Their aggression was context dependent. In the presence of equal size hamsters, they showed little aggression; however, they were excessively aggressive toward smaller, younger animals. Testosterone levels and reproductive behavior were normal after adolescent subjugation; however, release of cortisol during agonistic encounters was suppressed. In comparison, hamsters exposed to chronic social subjugation as adults had low plasma testosterone, reduced reproductive behavior, and exaggerated cortisol release during agonistic encounters. Self-ingestion of alcohol during adolescence enhanced testosterone release around the peripubertal period but reduced plasma testosterone levels in adulthood. Exposure to alcohol as adolescents enhanced aggression in adulthood. These data demonstrate a pronounced difference in behavior and neuroendocrinology between adolescent and adult hamsters in their response to traumatic stress.

Social experience and social context alter the behavioral response to centrally administered oxytocin in female Syrian hamsters

The type of social behavior displayed by an individual is profoundly influenced by its immediate social environment or context and its prior social experience. Although oxytocin is important in the expression of social behavior in several species, it is not known if social factors alter the ability of oxytocin to influence behavior. The purpose of the present study was to test the hypothesis that social experience and social context alter the ability of oxytocin to regulate flank marking (a form of scent marking) in female Syrian hamsters. Oxytocin was microinjected into the medial preoptic anterior hypothalamic continuum (MPOA-AH) of socially experienced, dominant female hamsters which were then tested with either a subordinate partner, with a novel partner, or alone. Oxytocin induced flank marking in a dose-dependent manner but only when the experienced dominant hamsters were tested with their familiar, subordinate partners. Oxytocin did not induce flank marking when injected into socially naive female hamsters that were tested with an opponent or alone. In males, by contrast, oxytocin induced flank marking in dominant hamsters when they were tested with their subordinate partner or alone. These data support the hypothesis that social experience and social context interact to regulate the ability of oxytocin to stimulate flank marking by its actions in the MPOA-AH in female hamsters.

Influence of social dominance on self-stimulation behavior in male golden hamsters

The effect of a socially dominant hamster on the self-stimulation behavior of the subordinate hamster was examined. After determining social ranking, six hamsters were trained to press a lever in an operant chamber in which a dominant hamster was presented over a grid wall. The threshold of rewarding effect was evaluated by using a descending series of current intensity as electrical reward. When a dominant hamster was present, the subordinate hamster showed a shift of intensity-response function to the right (higher intensity). The presence of a subordinate hamster did not influence the response in dominant hamsters. Furthermore, β-carboline (FG-7142) (5, 10, and 20 mg/kg, IP) caused a decrease in rewarding effect in dose-dependant manner. These results suggest that the presence of a dominant animal may have caused “a state of anxiety” somewhat similar to the anxiety caused by the benzodiazepine inverse agonist.

Vasopressin and serotonin interactions in the control of agonistic behavior

In hamsters, dominant/subordinate relationships are initially determined by overt aggression, but subsequently communicated by flank marking, an arginine vasopressin (AVP)-dependent behavior. Once a relationship is established, dominant males will flank mark at a higher frequency than their subordinate partners. Flank marking displayed during social encounters can be turned “on or off” by microinjection of AVP or AVP-receptor antagonist within the anterior hypothalamus (AH). For instance, microinjecting dominant hamsters with AVP-receptor antagonist blocks their flank marking and provokes an immediate induction of flank marking by subordinate animals. The central effects of AVP have been extended to include a role in offensive aggression. Microinjection of AVP-receptor antagonist into the AH inhibits the aggression of a resident hamster toward an intruder and diminishes aggression between hamsters placed into a neutral arena. Microinjection of AVP into the ventrolateral hypothalamus (VLH) facilitates offensive aggression of a resident toward an intruder. As AVP receptors in the VLH are testosterone-dependent, it is possible that the reduction of aggression observed in castrated hamsters is due to a loss of AVP responsiveness in the VLH. Recent work has focused on the notion that serotonin (5-HT) antagonizes AVP activity in the CNS. The AH and VLH have a high density of 5-HT terminals and binding sites. Indeed, there appear to be 5-HT synapses on AVP neurons in the AH. Microinjection of 5-HT into the AH inhibits AVP-induced flank marking while IP injection of fluoxetine a serotonin reuptake inhibitor inhibits AVP-induced offensive aggression in the VLH. It is possible that serotonin interacts with AVP to modulate offensive aggression.

Hormonal responses to fighting in hamsters: Separation of physical and psychological causes

Male Syrian hamsters were paired and allowed to interact with a conspecific for 15 min a day for 4 days. On the fifth day, the animals were again paired, but they were kept physically separated by a mesh partition that allowed visual, olfactory, and auditory contact between the animals. Controls were placed with conspecifics on each of the 5 testing days, but the partition between them was never removed. Hamsters that were submissive on days 1–4 exhibited elevated plasma adrenocorticotropin-like immunoreactivity (ACTH-LI), beta-endorphin-like immunoreactivity (B-EP-LI), and cortisol on day 5 even though no fighting occurred on that day. Dominant hamsters did not differ from controls. These data support the hypothesis that there is an important psychological component to the pituitary-adrenocortical response in defeated hamsters.

Effects of social conflict on POMC-derived peptides and glucocorticoids in male golden hamsters

The effects of fighting and footshock on circulating adrenocorticotropin-like immunoreactivity (ACTH-LI), cortisol, corticosterone, beta-endorphin-like immunoreactivity (β-EP-LI), and beta-lipotropin-like immunoreactivity (β-LPH-LI) were examined. In the first experiment, catheterized males were paired with large, ovariectomized females for 15 min. Submissive males exhibited significant increases in plasma ACTH-LI, cortisol, corticosterone, and β-EP-LI. In the second experiment, two males were paired to determine whether the hormonal response in submissive animals was different from that in dominant hamsters. The pattern and magnitude of the hormonal response was also compared to that following a commonly used stressor-footshock. Footshock was associated with large increases in each of the plasma hormones measured. Submission, but not dominance, was associated with smaller, but still significant, increases in ACTH-LI, cortisol, β-EP-LI, and β-LPH-LI. The data indicate that fighting is not a generalized stressor. “Losing,” in particular, appears to be an example of a biologically relevant stressor.

Vasopressin immunoreactivity in the anterior hypothalamus is altered during the establishment of dominant/subordinate relationships between hamsters

When paired for 15-min periods for 5–8 consecutive days, castrated, testosterone-treated hamsters consistently assumed the dominant status, based on a higher aggression index ( 18 ± 3) and frequency of flank marking ( 15 ±3) as compared to their castrated, untreated subordinate partners ( −1.3 ± 1 and 2.4 ± 1, respectively). In addition to these hamsters with established dominant/subordinate relationships, control hamsters with no social interactions were killed, and in all animals the vasopressin level in the anterior hypothalamus-medial preoptic area was assessed by counting vasopressin immuno-reactive perikarya following immunocytochemistry, or by radioimmunoassay of vasopressin from tissue punches. In the socialized pairs the subordinate hamsters had a significantly ( P < 0.01) lower number of vasopressin staining perikarya in the anterior hypothalamus, specifically the area of the nucleus circularis, than their dominant partners ( n = 6 pairs). There was also a significantly ( P < 0.001) lower level of vasopressin immunoreactivity in punches taken from the area of the nucleus circularis in subordinate hamsters as compared to their dominant partners ( n = 14 pairs). However, there were no significant differences in the number of perikarya or the concentration of immunoreactive vasopressin between subordinate and dominant hamsters in the supraoptic nucleus, paraventricular nucleus, suprachiasmatic nucleus or bed nucleus of the stria terminalis. The number of perikarya ( n = 5 pairs) and concentration of vasopressin ( n = 8 pairs) for all vasopressin immunoreactive sites, including the nucleus circularis, were similar for testosterone-treated and untreated hamsters that remained isolated and not subjected to daily aggressive encounters. The values in both groups of unsocialized hamsters were also similar to those seen in the testosterone-treated dominant hamsters. In summary, the only difference in the vasopressin level between dominant and subordinate hamsters was observed in the area of the nucleus circularis. Furthermore, the only group of hamsters that differed in both the number of vasopressin immunoreactive perikarya and concentration of vasopressin were castrated controls, i.e. subordinates, that were tested daily with highly aggressive testosterone-treated dominant hamsters. These data provide evidence showing (1) that the diminution in vasopressin immunoreactivity in subordinate hamsters occurs in response to repeated social encounters with aggressive dominant hamsters, (2) that a behavioral manipulation may contribute to changes in the neuroanatomy and/or chemistry of the central nervous system, and (3) that the vasopressinergic neurons of nucleus circularis may be involved in the control of vasopressin-dependent flank marking. The lower level of flank marking behavior in subordinate hamsters may reflect, in part, the level of vasopressin synthesis and release from this population of neurons.

A vasopressin antagonist can reverse dominant/subordinate behavior in hamsters

Golden hamsters communicate dominance status by flank marking, a behavior that is dependent upon vasopressin-sensitive neurons in the anterior hypothalamus-medial preoptic area (AH-MPOA). The purpose of the present study was to investigate whether arginine vasopressin (AVP) and an antagonist of AVP could alter or reverse dominant/subordinate relationships in pairs of hamsters. Microinjection of AVP into the AH-MPOA of subordinate hamsters dramatically increased their flank marking despite the presence of their dominant partners. Conversely, microinjection of the AVP antagonist into the AH-MPOA of dominant hamsters blocked flank marking in the presence of their subordinate partners. Surprisingly, the untreated subordinate hamsters significantly increased their own flank marking when tested with their dominant partners treated with the AVP antagonist, thereby reversing the pattern of flank marking normally seen in dominant/subordinate relationships. However, the effect of AVP and the AVP antagonist were limited to the day of treatment. When flank marking behavior was reversed in a pair of hamsters by treatments for three consecutive days, the pair immediately displayed the original dominant/subordinate behavior when treatment was stopped.

Characterization of dominant hamster cell mutants resistant to oxygenated sterols.

Stable mutants of Dede and CHO cells, resistant to suppression of cholesterogenesis by oxygenated sterols, have been isolated in a single step. Luria-Delbrück fluctuation analysis indicated a random occurrence of resistant at a rate of 1 x 10(-7) mutations/cell/generation. Cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and growth of the mutant cells were coordinately resistant to oxygenated sterols in the culture medium, and this resistance was expressed as a dominant trait in somatic cell hybrids of the wild-type and mutant cells. The dominant resistance was employed in the selection of various cells hybrids. There was complete additivity of reductase activities in mixed lysates of inhibited wild-type and uninhibited mutant cells, indicating that cytosolic (in)activation factors were not causative of this resistance. We suggest that oxygenated sterols are (co)repressors in suppression of the synthesis of the reductase and that the resistance mutant phenotypes result from altered regulatory loci.

Septal ablation and the social behavior of the golden hamster

In four experiments, the effect of septal ablation on the social behavior of the hamster was observed. The results indicated that septal ablation increased the aggressiveness of both socially naive and experienced dominant hamsters. If, however, the septal hamster experienced defeat by an opponent during preoperative testing, no postoperative increment in aggression was observed. All septal hamsters, whether aggressive or not, either ceased to display hoarding behavior or hoarded very little. All septal hamsters also showed persistent approach responses to their opponents. Paired contests between septal animals resulted in high levels of aggression with one septal in each pair being defeated and assuming a submissive status.