The Role of Oxytocin in the Stress and Anxiety Response.

Centrally released oxytocin (OT) is believed to attenuate stress-induced activation of the hypothalamic pituitary adrenal (HPA) axis as well as being anxiolytic. Therefore, it is expected that OT deficient (OT-/-) mice that do not synthesize or release OT centrally or peripherally will display enhanced HPA axis activation, as well as increased anxiety-related behavior compared to wildtype (OT+/+) mice. To test this hypothesis, OT-/- mice were exposed to shaker stress, (psychogenic stressor), cholecystokinin- (CCK) administration (physical stressor), or the elevated plus maze (EPM), a behavioral test of anxiety. Female OT-/- mice released more corticosterone than OT+/+ mice in response to shaker stress. Shaker stress exposure activated Fos in OT neurons of the paraventricular nucleus of the hypothalamus (PVN) of male and female OT+/+ mice and corticotropin-releasing hormone (CRH) within the PVN of male and female mice of both genotypes. In addition, shaker stress exposure revealed that Fos expression in the medial nucleus of the amygdala (MeA) was lower in female OT-/- than OT+/+ mice. Genotypic differences in corticosterone release and Fos activation of the MeA in response to shaker stress exposure were not observed in male mice. Furthermore, similar genotypic (and/or sex) differences were not revealed in response to CCK-administration. OT is also anxiolytic in female mice. Female OT-/- mice tested in the EPM displayed increased anxiety-related behavior compared to OT+/+ mice. In response to EPM exposure Fos expression in the MeA was greater in female OT-/- mice than OT+/+ mice. Surprisingly, male OT-/- mice tested in the EPM displayed decreased anxiety-related behavior compared to OT+/+ mice, but did not display genotypic differences in the Fos expression within the MeA. The results of this thesis suggest that OT is anxiolytic and attenuates HPA activation in female, but not male mice. Furthermore, it appears that OT plays a modulatory role in the processing of psychogenic stressors, but may not be involved in the processing of physical or systemic stressors. More specifically, it is possible that OT plays a role in behavioral and physiological responses that depend upon neuronal processing within the MeA