Mapping Brain Response to Social Stress in Rodents With c-fos Expression: A Review

Abstract

Social defeat is an important event in the life of many animals, and forms part of the process of social control. Adapting to social defeat is thus an intrinsic part of social "homeostasis", and mal-adaptation may have pathological sequelae. Experimental models of social defeat (e.g. inter-male aggression) have existed for many years. However, very few studies have investigated the changes in brain activity in male animals exposed to the social stress of being defeated by another conspecific male, and in all these studies the expression of the immediate-early gene c-fos has been used as the marker of neuronal activity. In general, the results obtained inform that many areas of the brain, especially those involved in the general stress response, increase their activity when animals are exposed to an acute defeat. However, when animals are defeated repeatedly over many consecutive days, the level of activation of the brain shows different patterns of adaptation depending on the brain areas (varying from complete habituation to persistent activation). Discrepancies between studies may be due to differences in the experimental procedure. On the other hand, further research has to be conducted in order to understand what these changes in the brain activity mean in relation to the other stress responses to social defeat. Furthermore, knowing that the corresponding protein products of many immediate-early genes are transcription factors that can promote or inhibit the expression of target genes, research following this approach is also necessary.

Methylmercuric chloride induces activation of neuronal stress circuitry and alters exploratory behavior in the mouse

“…While open field exposure per se likely involves induction of a fear-like state due to the unfamiliar circumstances, the lack of a significant c-Fos increase may be due to insufficient intensity of this psychogenic stressor. Indeed, in other studies it has been shown that c-Fos is reliably increased in the CeC in response to a variety of psychological stressors (Pacak et al, 1995,Senba and Ueyama, 1997,Martinez et al, 2002,Rossi-George et al, 2005. Nonetheless, CeC activation by MeHg suggests engagement of neural substrates necessary for adaptational physiological and behavioral responses, and is consistent with the significant reduction in exploratory behavior observed in MeHg treated mice.…”

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

“…Social stress-induced alterations of gene expression in limbic areas are involved in long-term neuroadaptations and behavioral impairments (Martinez et al, 2002). Interestingly, a number of reports linked BDNF neurotransmission in the neuropathophysiology of psychiatric disorders in general (Balaratnasingam and Janca, 2012) and depression in particular (Duman and Monteggia, 2006).…”

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes

“…For example, the BNST is activated by acute stressors (Bonaz and Tache 1994;Campeau and Watson 1997;Kollack-Walker et al 1997;Martinez et al 1998Martinez et al , 2002, likely from excitatory glutamatergic and/or CRF-containing inputs from the amygdala, ventral subiculum and limbic cortices, and is essential for stress-induced learning (Bangasser et al 2005). Chronic stress, which is known to produce depressive-like symptoms such as anhedonia, elevates levels of CRF in the BNST (Chappell et al 1986;Stout et al 2000).…”