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 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)