DIVERGENT PROLACTIN AND PITUITARY-ADRENAL ACTIVITY IN RATS SELECTIVELY BRED FOR DIFFERENT DOPAMINE RESPONSIVENESS

The present study explores the significance of brain dopamine phenotyp e for individual variation in the neuroendocrine stress response of th e rat. For this purpose, we used two Wistar rat lines previously selec ted for high or low responsiveness of the dopamine system to apomorphi ne using the gnawing response as the selection criterion. Systemic adm inistration of the drug evoked in apomorphine-susceptible (apo-sus) ra ts a vigorous gnawing response, whereas apomorphine-unsusceptible lapo -unsus) rats did not gnaw under these conditions. These two rat lines represent individuals displaying extreme differences in gnawing behavi or that otherwise coexist in a normal Wistar population. In this study basal and stress-induced hypothalamic-pituitary-adrenal activity and PRL release were measured in chronically cannulated, freely moving rat s that endured a conditioned emotional response. Tyrosine hydroxylase messenger RNA (mRNA), corticosteroid receptor mRNA, and in vivo retent ion of [H-3]corticosterone were measured in rat brain sections using i n situ hybridization and in vivo autoradiography. The results show tha t 1) apo-sus rats had a markedly reduced PRL response to stress compar ed to apo-unsus animals, whereas basal levels were not significantly d ifferent. A12 dopaminergic neurons in the arcuate nucleus expressed si gnificantly higher levels of tyrosine hydroxylase mRNA in apo-sus rats , suggesting that the reduced stress-induced PRL release could be due to an increased inhibitory control by dopaminergic neurons; 2) in apo- sus rats, stress resulted in a sustained elevation of ACTH and free co rticosterone levels, whereas the total corticosterone levels were not different between the two rat lines; 3) under basal morning conditions , apo-sus rats had significantly higher plasma ACTH, but, in contrast, lower free corticosterone than apo-unsus rats; total plasma corticost erone levels were not different; 4) the basal evening ACTH level was e levated in apo-sus rats; after removal of the adrenals in the morning, this increased ACTH level in apo-sus mts persisted into the afternoon 6 h postadrenalectomy; and 5) hippocampal mineralocorticoid (MR), but not glucocorticoid (GR), receptor capacity was increased in apo-sus r ats, with the affinity of both receptors for the ligand comparable bet ween the groups; the MR of apo-sus rats displayed an increased retenti on of [H-3]corticosterone in all hippocampal cell fields measured 24 h after adrenalectomy; MR and GR mRNA in hippocampus as well as GR mRNA in the paraventricular nucleus were not significantly different in th e two rat lines. In conclusion, the data suggest; a common genetic bac kground for individual variation in stress responsiveness and dopamine phenotype. High dopamine reactivity is linked to a reduced PRL and an increased ACTH response after stress. These high dopamine responders display a hyporesponsive adrenal cortex and corticosteroid feedback re sistance associated with altered brain corticosteroid receptor propert ies.