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Victims of aggression: Psychological and biological consequences
Organizers: Manuela Martinez, University of Valencia and Queen Sofia Center for the Study of Violence, Valencia, Spain
Paul F. Brain, University of Wales Swansea, UK

This symposium illustrates that the changes induced by experiencing defeat and/or subordination in male rodents are more detrimental than following more conventional stressors as well as being influenced by genetic factors. Recovery from such experiences is influenced by living conditions and individual differences in stress-responsiveness. Neural activities in the forebrain and brainstem show patterns of adaptation with repeated defeats. Subordination impairs reproduction and causes atherosclerosis in female macaques. A re- evaluation of loss of status as an animal model of anxiety or depression is provided along with details of changes in a variety of receptor systems as well as alterations in neuronal plasticity.

The importance of social housing in social defeat induced changes in behavior and HPA regulation
J.M. Koolhaas, B. Buwalda, M.A.W. Ruis, and S.F. de Boer (University of Groningen, The Netherlands)
Social defeat induces a gradually developing change in HPA axis regulation at various levels of organization in the course of weeks. Studies indicate that this dynamic change in HPA axis regulation only develops when the animals are socially isolated after the defeat.

The impact of social defeat on cardiac activity in rats
A. Sgoifo, S. F. de Boer, B. Buwalda, F. Maes, and J.M. Koolhaas
(University of Groningen, The Netherlands)
Sympatho-vagal interaction and susceptibility to cardiac arrhythmias were studied in wild-type rats by analyzing telemetry ECG recordings obtained during social defeat and other non-social stressors (restraint, shock prod test, swimming). Defeated rats showed much larger heart rate accelerations, much lower values of heart rate variability, and far more recurrent cardiac arrhythmias (mostly ventricular extrasystoles), which all together point to a shift of autonomic balance towards a marked sympathetic dominance. Therefore, social aversive contexts are potentially more detrimental to cardiac electrical stability than other non-social aversive stimuli.

Adaptation in patterns of c-fos expression in the brain of male rats by repeated exposure to social defeat
M. Martinez (University of Valencia and The Queen Sofia Center for the Study of Violence, Valencia, Spain)
J. Herbert (University of Cambridge, Cambridge, UK)
F. Martinez-Soriano and A. Calvo-Torrent  (University of Valencia, Valencia, Spain)
K.K. Chung (University of Cambridge, Cambridge, UK)
A. A. Valverde, J. L. Paya-Cano and M.A. Pico-Alfonso (University of Valencia, Valencia, Spain)
C-fos expression was used to map the pattern of neural activation following either a single or repeated defeat in male rats. After a single defeat c-fos expression was intense in different forebrain and brainstem areas. However, after the tenth defeat, this pattern was modified. In a posterior study, depletion of 5-HT did not affect the neural pattern of adaptation. Another study is being conducted in which animals are exposed to 1, 2, 5, 10 or 20 consecutive defeats, being the pattern of c-fos expression currently analyzed.(back to top)

Development of psychopathological states induced by repeated social defeats in male mice: Strain differences
N. Kudryavtseva
(Institute of Cytology and Genetics SD RAS, Novosibirsk, Russia)
Heredity plays a substantial role in the etiology of many psychoses. It is generally agreed that it is not the disease that is inherited, but a predisposition to it. Environmental factors, often of psychogenic nature, determine the probability of development of psychopathologies. A comparative analysis of the respective features of behavioral and physiological reactions to repeated experience of defeats in C57BL/6J mice with a genetic predisposition to develop a depression-like state and CBA/Lac mice with genetic predisposition to catalepsy is described.(back to top)

Changes in brain serotonergic activity in anxious losers
D. Avgustinovich, D. Lipina, O. Alekseyenko, N. Kudryavtseva
(Institute of Cytology and Genetics SD RAS, Novosibirsk, Russia)
Repeated experience of defeats in 10 daily agonistic confrontations produced pronounced anxiety in C57BL/6J male mice (defeated, losers). The anxiety was associated with changes in the levels of 5-HT and 5-HIAA as well as in TPH activity in some brain regions of losers. Moreover, it was found a reduced 5-HT1A receptor sensitivity in the anxious losers. The data obtained show that pronounced anxiety was accompanied by differential changes of serotonergic activity in the varied brain areas.(back to top)

Involvement of brain D1 and D2 dopamine receptors in development of depression-like state resulting from repeated social confrontations in male mice
O. Alekseyenko, D. Avgustinovich, and T. Lipina
(Institute of Cytology and Genetics SD RAS, Novosibirsk, Russia)
Brain D1 and D2 receptors were investigated in male mice with repeated experience of social defeats inducing a depression-like state. Losers after 10 and 20 days of agonistic confrontations were studied. Effects of D1/D2 antagonist cis-fluphentixol and D2 antagonist sulpiride were investigated in behavioral tests. The data obtained showed that development of "depression" is accompanied by D1 receptor sensitivity changes. A [3H]SCH 23390 binding assay supported these results.(back to top)

Long-lasting adaptations in opiodergic and aminergic neurons after brief social defeat
E.M. Nikulina, J. E. Marchand, R. M. Kream, and K.A. Miczek (Tufts University, Boston, MA)
Fos-like immuhohistochemistry (Fos-LI) in periaqueductal gray matter, dorsal raphe, and locus coeruleus was significantly increased after social defeat stress induced by a short confrontation with an experienced aggressive resident. Social stress produced a gradual decline in the expression of preproenkephalin mRNA and increased expression of mu opioid receptor and preprotachykinin mRNAs in periaqueductal grey matter. Exposure to social defeat had enduring consequences on Fos-LI response to psychostimulants as morphine and cocaine.(back to top)

Recovery following chronic subordination stress in rats
M.A. Hebert, R. Sakai, C. McKittrick, and R.J. Blanchard
(University of Hawaii at Manoa, Honolulu, HI, USA)
Subordinate rats placed in mixed-sex colonies for two weeks exhibited disturbances in behavior, physiology, and neuroendocrine function. In order to investigate possible recovery of function, colonies were disbanded for two weeks. During this period, subordinates exhibited rapid recovery of body weight, increases in basal testosterone and corticosterone, and reinstatement of corticosterone responsiveness to acute stress. Thymus weights failed to recover in severely stressed animals, suggesting residual effects that enhance susceptibility to future stressors.(back to top)

The physiologic consequences of subordinate social status in groups of female macaques
J.R. Kaplan (Wake Forest University, Winston-Salem, NC)
S. B. Manuck (University of Pittsburgh, Pittsburgh, PA)
M.R. Adams (Wake Forest University, Winston-Salem, NC)
When living in small (n<6), isosexual social groups, female Cynomolgus macaques (Macaca fasicularis) ranked below the median experience significant reproductive impairment relative higher ranking animals. Subordinate females also exhibit hypercortisolemia. Among the pathobiologic sequelae of these physiologic states is an increased susceptibility to coronary artery atherosclerosis. A related observation is that females develop a hormonal (and disease) profile that reflects their current rank; changes in rank precede and do not follow changes in hormonal status. (back to top)

Further evaluation of loss of status as an animal model of depression
P.F. Brain and L. P. Marrow
(University of Wales Swansea, UK)
Six pairs of male Lister hooded rats were observed in videotaped biweekly one hour sessions. Dominant animals of 5 stable pairs were home-cage defeated weekly, by singly housed TMD rats in taped encounters. After 5 weeks of defeat, all 5 'dominant' animals showed changed behavior. However, social status reversal between resident pairs occurred only in 2 cases. Only in 2 cases was there a status reversal. All defeated animals (regardless of whether defeat affected status), received daily imipramine injections (5mg/kg) for 5 subsequent weeks. Far from reversing or improving the status, imipramine made animals more likely to lose encounters with cage mates.(back to top)