106. Behavioural and somatic mal-adaptations after chronic psychosocial stress: Reversal by chronic oxytocin?

Abstract

Chronic psychosocial stress is an accepted risk factor for various affective and somatic disorders. In an established murine chronic stress model, chronic subordinate colony housing (CSC) results in the alteration of physiological, behavioural, neuroendocrine and immunological parameters (1). Accompanied by thymus atrophy and adrenal hypertrophy as indicators of chronic stress, CSC mice show impaired glucocorticoid signalling and increased pro-inflammatory cytokine secretion from mesenteric lymph node cells (mesLNC), all contributing to CSC-induced spontaneous colitis, aggravation of chemically induced colitis and the enhanced risk for developing colorectal cancer (2). Further, CSC mice show a long-lasting increase in general anxiety, whereas, in contrast, depression-related behaviours remain unchanged (3). First experiments indicate that chronic icv administration of oxytocin, a neuropeptide with anxiolytic and anti-stress effects (4), via osmotic minipumps during CSC exposure dose-dependently affects some of the CSC-induced consequences. For example, at low dose (1 ng/h), chronic oxytocin prevented thymus atrophy, adrenal hypertrophy and the interferon gamma hyper secretion from mesLNC. In contrast, chronic high doses of oxytocin (10 ng/h) increased anxiety-related behaviour in unstressed mice and reduced oxytocin receptor binding in limbic brain areas. Thus, administration of oxytocin during ongoing chronic stress seems to partly prevent stress-induced mal-adaptations. 1 Reber S et al. Endocrinology 2007, 148:670–82. 2 Peters S et al. Stress 2012, 15:403–15 3 Slattery DA et al. Psychoneuroendocrinology 2012, 37:702–14 4 Neumann ID and Landgraf R. TINS 2012, 35:649–659