Dopamine susceptibility of APO-SUS rats is not per se coupled to HPA-axis activity

Abstract A synergistic relationship is thought to exist between hypothalamic–pituitary–adrenal (HPA) axis activity and dopamine neurotransmission. To test whether a high response to dopamine indeed implies a hyperactive HPA-axis, we here used Wistar rats that were selected twice independently (original and replicate lines) for a high or low susceptibility to the dopamine receptor agonist apomorphine (so-called APO-SUS and APO-UNSUS rats, respectively). The APO-SUS rats from the original line displayed a hyperactive HPA-axis in that higher basal and stress-induced adrenocorticotropic hormone (ACTH) levels, and lower basal free-corticosterone levels were observed than those found in the original APO-UNSUS rats. In contrast, the activity of the HPA-axis in the APO-SUS rats from the replicate line did not differ from that in the replicate APO-UNSUS rats. Thus, in the APO-SUS/APO-UNSUS rat model the level of HPA-axis activity is not necessarily causally linked to dopamine responsiveness, implying that a hyperactive HPA-axis is not a prerequisite for a high dopaminergic response.