Differential expression of c-fos mRNA within neurocircuits of male hamsters exposed to acute or chronic defeat.

Chronic exposure to stress has been implicated in physical and mental illness, and such experiences can produce alterations in the connectivity and number of neurones within the brain to variations in the expression of specific genes. The purpose of this study was to determine how repeated exposure to social defeat affects neuronal activation patterns within the male Syrian hamster brain. Toward this end, the levels c-fos mRNA were compared among three groups: (1) handled controls (HC); (2) acutely defeated males (AD); and (3) chronically defeated males (15 min aggression daily, 7 days) exposed to an acute challenge (CD). Plasma glucocorticoids were also measured and compared among groups as an index of neuroendocrine activity. The results show a selective pattern of habituation of immediate early gene expression within the brains of chronically defeated males. In particular, c-fos mRNA levels were significantly decreased within the paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus of the hypothalamus, septohypothalamic nucleus, intermediate subdivision of the lateral septum, central amygdaloid nucleus, and the amygdalohippocampal area in the CD group exposed to an acute challenge when compared to males defeated only once. In contrast, c-fos expression within the anterior and ventromedial nuclei of the hypothalamus, dorsal periaqueductal grey, dorsal raphe, cuneiform nucleus, and locus coeruleus did not differ between AD and CD groups. Similarly, plasma levels of cortisol and corticosterone in CD group were equivalent to those observed after a single defeat experience. We discuss the possibility that decreased expression of c-fos mRNA within the PVN and other brain regions of defeated animals-in the presence of elevated adrenal steroids-may reflect a state of molecular plasticity that could alter neurotransmission within the limbic-hypothalamo-pituitary-adrenocortical axis. In contrast, brain areas that maintain relatively high levels of c-fos mRNA following repeated defeat may reflect processes less likely to adapt such as defensive behaviour.