Hatano high (HAA)- and low (LAA)-avoidance rats are two lines of Sprague-Dawley rats genetically selected on the basis of their active avoidance behavior in a shuttle-box. They also differ in several other behavioral responses, such as their locomotors activity in novel environments (open-field, circular corridor), with the HAA rats being more active than the LAA animals, as well as in endocrine reactivity, immune functions and stress response. We therefore set out to investigate the adrenal endocrinology of the HAA and LAA strains. It was found that the LAA rats had a significantly blunted ACTH response to restraint stress compared with HAA, but higher corticosterone and prolactin (PRL) response. This finding suggested that the HAA adrenal is less sensitive to ACTH than LAA. This was confirmed by investigating the corticosterone dose response to ACTH in adrenals from the two strains incubated in vitro. Several possible intra-adrenal regulators were investigated. The level of expression of steroidogenic acute regulatory (StAR) and long form of PRL receptors (PRLR-L) mRNA were higher in LAA rats as compared with HAA rats, but lower expression of melanocortin-2 receptors (MC2R) and CYP11A1 mRNA. These finding clearly demonstrate that the adrenals of the HAA strain have a diminished sensitivity to stimulation with ACTH, while the LAA have increased sensitivity. We purpose that PRL is responsible for increasing adrenocortical responses to ACTH stimulation in the LAA strain. The observed changes in adrenal sensitivity to ACTH suggest that this rat strain may have considerable implications for the animals' adaptive stress response.
