Divergent prolactin and pituitary-adrenal activity in rats selectively bred for different dopamine responsiveness

被引:57
作者
Rots, NY
Cools, AR
Oitzl, MS
DeJong, J
Sutanto, W
DeKloet, ER
机构
[1] LEIDEN UNIV,DIV MED PHARMACOL,CTR BIOPHARMACEUT SCI,LEIDEN AMSTERDAM CTR DRUG RES,2300 RA LEIDEN,NETHERLANDS
[2] UNIV NIJMEGEN,DEPT PSYCHONEUROPHARMACOL,NIJMEGEN,NETHERLANDS
关键词
D O I
10.1210/en.137.5.1678
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The present study explores the significance of brain dopamine phenotype for individual variation in the neuroendocrine stress response of the rat. For this purpose, we used two Wistar rat lines previously selected for high or low responsiveness of the dopamine system to apomorphine using the gnawing response as the selection criterion. Systemic administration of the drug evoked in apomorphine-susceptible (apo-sus) rats 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 behavior 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 rats that endured a conditioned emotional response. Tyrosine hydroxylase messenger RNA (mRNA), corticosteroid receptor mRNA, and in vivo retention of [H-3]corticosterone were measured in rat brain sections using in situ hybridization and in vivo autoradiography. The results show that 1) apo-sus rats had a markedly reduced PRL response to stress compared to apo-unsus animals, whereas basal levels were not significantly different. A12 dopaminergic neurons in the arcuate nucleus expressed significantly 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 corticosterone 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 corticosterone levels were not different; 4) the basal evening ACTH level was elevated 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 rats, with the affinity of both receptors for the ligand comparable between the groups; the MR of apo-sus rats displayed an increased retention 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 the two rat lines. In conclusion, the data suggest; a common genetic background 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 resistance associated with altered brain corticosteroid receptor properties.
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页码:1678 / 1686
页数:9
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