Aaron M. Jasnow

Conditioned defeat in male and female Syrian hamsters

A brief exposure to social defeat in male Syrian hamsters (Mesocricetus auratus) leads to profound changes in the subsequent agonistic behavior exhibited by the defeated animals. Following defeat in the home cage of an aggressive conspecific, male hamsters will subsequently fail to defend their home territory even if the intruder is a smaller, nonaggressive male. This phenomenon has been called conditioned defeat. In Experiment 1, we examined the duration of conditioned defeat by repeatedly testing (every 3-5 days) defeated hamsters with a nonaggressive intruder. We found that conditioned defeat occurs in all defeated male hamsters and persists for a prolonged period of time (at least 33 days) in the majority of male hamsters tested despite the fact that these animals are never attacked by the nonaggressive intruders. In Experiment 2, we examined whether conditioned defeat could be induced in female Syrian hamsters. While conditioned defeat occurred in some females, they displayed only low levels of submissive/defensive behavior and, in contrast to males, the conditioned defeat response did not persist beyond the first test. These results suggest that in male hamsters conditioned defeat is a profound, persistent behavioral change characterized by a total absence of territorial aggression and by the frequent display of submissive and defensive behaviors. Conversely, social defeat in female hamsters does not appear to induce long-term behavioral changes. Finally, in Experiment 3, we determined that plasma adrenocorticotropin-like immunoreactivity increases in females following social defeat in a manner similar to that seen in males, suggesting that the disparate behavioral reactions of males and females are not due to sex differences in the release of, or response to, plasma adrenocorticotropin.

Short-day increases in aggression are inversely related to circulating testosterone concentrations in male Siberian hamsters (Phodopus sungorus).

Many nontropical rodent species display seasonal changes in both physiology and behavior that occur primarily in response to changes in photoperiod. Short-day reductions in reproduction are due, in part, to reductions in gonadal steroid hormones. In addition, gonadal steroids, primarily testosterone (T), have been implicated in aggression in many mammalian species. Some species, however, display increased aggression in short days despite basal circulating concentrations of T. The goal of the present studies was to test the effects of photoperiod on aggression in male Siberian hamsters (Phodopus sungorus) and to determine the role of T in mediating photoperiodic changes in aggression. In Experiment 1, hamsters were housed in long and short days for either 10 or 20 weeks and aggression was determined using a resident-intruder model. Hamsters housed in short days for 10 weeks underwent gonadal regression and displayed increased aggression compared to long-day-housed animals. Prolonged maintenance in short days (i.e., 20 weeks), however, led to gonadal recrudescence and reduced aggression. In Experiment 2, hamsters were housed in long and short days for 10 weeks. Half of the short-day-housed animals were implanted with capsules containing T whereas the remaining animals received empty capsules. In addition, half of the long-day-housed animals were castrated whereas the remaining animals received sham surgeries. Short-day control hamsters displayed increased aggression compared to either castrated or intact long-day-housed animals. Short-day-housed T treated hamsters, however, did not differ in aggression from long-day-housed animals. Collectively, these results confirm previous findings of increased aggression in short-day-housed hamsters and suggest that short-day-induced increases in aggression are inversely related to gonadal steroid hormones.

Activation of GABAA receptors in the amygdala blocks the acquisition and expression of conditioned defeat in Syrian hamsters

Social defeat is a powerful experience that often leads to drastic physiological and behavioral changes in many animal species. An example of such a change is conditioned defeat in Syrian hamsters. The neurophysiological mechanisms that underlie such changes are not yet fully understood, however, there is evidence that the amygdala plays an essential role in behavioral and emotional responses to a variety of stressors. The goal of the present study was to determine whether GABAergic neurotransmission in the amygdala is a critical component of conditioned defeat in male Syrian hamsters. Experiment 1 examined whether infusion of the GABA(A) receptor agonist, muscimol (0.0, 4.4, 8.8 nmol), into the amygdala would block the acquisition of conditioned defeat. Experiment 2 examined whether infusion of muscimol into the amygdala prior to testing would block expression of conditioned defeat. Submissive behavior during testing was significantly reduced in animals receiving infusions of muscimol immediately prior to initial defeat training. Animals that received infusions of muscimol immediately prior to being tested with a non-aggressive intruder also displayed significantly less submissive behavior than did animals receiving vehicle control. These data indicate that infusion of muscimol into the amygdala can block the acquisition and expression of conditioned defeat, a finding that indicates that GABAergic neurotransmission within the amygdala is involved in the acquisition and expression of fear or stress-induced behavioral changes. This is the first evidence indicating that the neural circuits involved in Pavlovian fear conditioning are also involved in more ethologically-relevant models examining stress-related behavioral plasticity.

Involvement of Central Amygdalar and Bed Nucleus of the Stria Terminalis Corticotropin-Releasing Factor in Behavioral Responses to Social Defeat

The authors investigated whether corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST) is a critical component of the neural circuitry mediating conditioned defeat. In this model, hamsters that have experienced social defeat subsequently display only submissive-defensive agonistic behavior instead of territorial aggression. Conditioned defeat was significantly reduced following infusion of the CRF receptor antagonist D-Phe CRF((12-41)) into the BNST but not into the CeA. In another experiment, hamsters given unilateral lesions of the CeA and infusions of D-Phe CRF((12-41)) into the contralateral BNST displayed significantly less submissive behavior than did controls. These data suggest that CRF acts within a neural circuit that includes the amygdala and the BNST to modulate agonistic behavior following social defeat.

Differential effects of two corticotropin-releasing factor antagonists on conditioned defeat in male Syrian hamsters (Mesocricetus auratus).

The purpose of the present study was to determine whether corticotropin-releasing factor (CRF) is involved in mediating the expression of conditioned defeat in male Syrian hamsters. The present study examined the effects of two different competitive CRF receptor antagonists on the expression of conditioned defeat. Specifically, Experiment 1 examined whether peripheral administration of CP-154,526, a specific non-peptide CRF1 receptor antagonist, would reduce the expression of conditioned defeat. Experiment 2 examined whether D-Phe CRF(12-41), a nonspecific CRF1/CRF2 receptor antagonist, infused directly into the brain, would reduce the expression of conditioned defeat. The results revealed that i.p. injections of CP-154,526 did not reduce the expression of conditioned defeat, whereas i.c.v. injections of D-Phe CRF(12-41) successfully reduced the expression of conditioned defeat. The duration of submissive/defensive behaviors in hamsters that received the high dose of D-Phe CRF(12-41) was significantly less than that exhibited by animals that received a vehicle control. The present data suggest that central CRF may be involved in mediating the expression of conditioned defeat and other behavioral responses to stressful stimuli.

Acute and chronic social defeat suppresses humoral immunity of male Syrian hamsters (Mesocricetus auratus).

Stressors, both physical and psychological, can activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to a wide range of physiological responses including increased glucocorticoid release and suppression of immune function. The majority of studies published to date have focused on the effects of physical stressors (e.g., cold exposure, electric shock) on immunity. The present study examined the role of a stressor, social defeat, on humoral immune function of Syrian hamsters (Mesocricetus auratus). Specifically, adult male Syrian hamsters experienced social defeat (i.e., exposure to a dominant animal in that animals home cage) that was either acute (i.e., a single exposure) or chronic (i.e., daily exposures across 5 days). A control group of animals was placed in a residents home cage without the resident animal present and did not experience defeat. After the last encounter, blood samples were drawn and animals were subsequently injected with keyhole limpet hemocyanin (KLH). Blood samples were again taken 5 and 10 days postimmunization and serum was analyzed to determine serum cortisol and anti-KLH immunoglobulin G (IgG) concentrations. Cortisol concentrations were elevated in both acutely and chronically defeated hamsters compared with control animals. In contrast, serum IgG concentrations were significantly reduced in both groups of defeated hamsters compared with control animals. Collectively, these results demonstrate that both acute social defeat and chronic social defeat lead to activation of the HPA axis and suppression of humoral immune function. These data suggest that social defeat is an important, ecologically relevant model with which to examine stress-induced immune suppression in rodents.

Memory of social defeat is facilitated by cAMP response element-binding protein overexpression in the amygdala.

The cAMP-responsive element binding protein (CREB) is a transcription factor that regulates synaptic plasticity and memory formation. Studies that have used conditioned fear models have established that CREB is important for the acquisition and consolidation of fear learning. The authors demonstrate that overexpression of CREB within the basolateral amygdala (BLA) of animals that are exposed to social defeat enhances subsequent defeat-induced changes in social behavior. This effect is specific to the acquisition of defeat-induced behaviors; overexpression of CREB has no effect on the expression of these behaviors if the overexpression occurs after the initial defeat. These data demonstrate that CREB is important for regulating learning not only to explicit cues but also for mediating behavioral plasticity in ethologically relevant social contexts.

Exposure to short days, but not short‐term melatonin, enhances humoral immunity of male Syrian hamsters (Mesocricetus auratus)

Abstract: Many non‐tropical rodent species rely on photoperiod as the primary cue to co‐ordinate seasonally appropriate changes in physiology and behavior. Among these seasonal changes, several rodent species (e.g. deer mice, prairie voles, Siberian hamsters) adjust immune function in response to changes in ambient day lengths. The goals of the present study were to examine the effects of photoperiod on immune function of Syrian hamsters (Mesocricetus auratus), and to determine the role of melatonin in mediating photoperiodic changes in immunity. In Experiment 1, male Syrian hamsters were housed in long (LD 14:10) or short days (LD 10:14) for 10 wk. In Experiment 2, hamsters were housed in long days and half of the animals were given 10 consecutive days of i.p. melatonin injections (15 μg) in the early evening, while the remaining animals received injections of the vehicle alone. After the respective experimental manipulations, animals were injected with the antigen, keyhole limpet hemocyanin (KLH), blood samples were obtained and anti‐KLH IgG antibody production was assessed. In Experiment 1, short‐day hamsters underwent gonadal regression and reduced serum testosterone as well as displayed increased humoral immune function compared with long‐day animals. In Experiment 2, short‐term melatonin treatment did not affect gonadal mass, testosterone or humoral immune function. These results confirm previous findings of photoperiodic changes in immunity in rodents and suggest that changes in humoral immunity are not due to short‐term changes in melatonin.

Glutamic acid decarboxylase mRNA in the suprachiasmatic nucleus of rats housed in constant darkness.

This study demonstrates that the levels of the mRNAs encoding the two isoforms of glutamic acid decarboxylase (GAD) (i.e., GAD65 and GAD67) do not differ over the circadian activity cycle in the suprachiasmatic nucleus (SCN) of rats housed in constant darkness. These data indicate that the rhythmic expression of GAD56 mRNA previously observed in animals housed in a light:dark cycle [K.L. Huhman, A.C. Hennessey, H.E. Albers, Rhythms of glutamic acid decarboxylase mRNA in the suprachiasmatic nucleus, J. Biol. Rhythms 11 (1996) 311-316.] is the result of the activity of retinal afferents.

Sympathoadrenal System Differentially Affects Photoperiodic Changes in Humoral Immunity of Siberian Hamsters (Phodopus sungorus)

Siberian hamsters (Phodopus sungorus) rely on photoperiod as a primary cue to coordinate seasonally appropriate changes in physiology and behaviour. Among these seasonal changes is reduced immune function in short ‘winter‐like’ days, compared to long ‘summer‐like’ days. Previous evidence suggests that immune function is regulated, in part, by the sympathoadrenal system. The precise role of the sympathoadrenal system in regulating photoperiodic changes in immune function, however, remains unspecified. The goal of the present study was to examine the differential contributions of direct sympathetic innervation of immune target tissue, as well as adrenal medullary catecholamines, to photoperiodic changes in immune function in male Siberian hamsters. In Experiment 1, hamsters underwent either bilateral surgical removal of the adrenal medulla (ADMEDx), or sham surgeries, and were maintained in long (LD 16 : 8) or short days (LD 8 : 16). In Experiment 2, hamsters received either surgical denervation of the spleen, or sham surgeries, and were then housed in long or short days. Serum anti‐KLH IgG concentrations and splenic norepinephrine (NE) content were determined in both experiments. Short‐day hamsters had reduced humoral immunity compared to long‐day hamsters. ADMEDx reduced immune function, but only in long‐day hamsters. In contrast, splenic denervation reduced humoral immunity, but only in short‐day hamsters. Splenic NE content was increased in short days and by ADMEDx. NE content was markedly reduced in denervated hamsters compared to sham‐operated hamsters. Collectively, these results suggest that the sympathoadrenal system is associated with photoperiodic changes in immune function.