The purpose of these studies was to determine the role of estrogen (E) and N/OFQ on the stress-induced increase in circulating prolactin (PRL) levels and on the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, the effect of experimental conditions, including serial sampling, handling and surgery on the activation of the HPA axis was investigated.
In both males and females, pretreatment with the N/OFQ receptor antagonist Comp B had no effect on HPA axis activation as determined by the corticosterone (CORT) response, but attenuated the PRL increase following stress. These results indicate that N/OFQ is involved in mediating the stress-induced PRL response, but not HPA activation. There was a gender difference in the PRL response, with the increase being significantly greater in females than in males. This gender difference was due, at least in part, to Estrogen since the PRL increase in ovariectomized (OVX) female rats that had estrogen replacement had a significantly greater response to stress than placebo treated animals. Furthermore, stress produced a significant increase in PRL-R expression in the choroid plexus of intact females, but not males, and this was blocked by pretreatment with Comp B. Although Comp B administration had no effect on basal, circulating PRL levels, it caused a 30% reduction in the PRL-R expression levels in the choroid plexus in intact females, suggesting N/OFQ may be involved in mediating PRL-R expression under resting conditions in females only. Additionally, PRL-R expression was significantly greater in Ovx+E treated females than in placebo treated controls.
Finally, these findings demonstrate that when designing experiments to investigate the effects of stress, experimental conditions alone may activate the highly sensitive HPA axis. Therefore, it is important to determine the effects of experimental conditions, e.g. surgical interventions, injection and sampling methods to distinguish between the effects of the specific stress and experimental conditions.