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

Abstract

The present study explores the significance of brain dopamine phenotype for individual variation in the neuroendocrine stress re sponse of the rat. For this purpose, we used two W istar ra t 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 (apo-unsus) rats did not gnaw under these conditions. These two rat lines represent individuals displaying extreme differences in gnawing behavior th at otherwise coexist in a normal Wistar population. In this study basal and stressinduced hypothalamic-pituitary-adrenal activity and PRL release were m easured 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 [3H]corticosterone were measured in ra t brain sections using in situ hybridization and in vivo autoradiography.The results show th at 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 th at the reduced stress-induced PRL release could be due to an increased inhibitory R ECENT STUDIES have shown that dopamine is linked to stress. For instance, stress induces a PRL response, and this release of PRL is under inhibitory control of dopa mine (1-3). Furthermore, rats with a predisposition to de velop amphetamine self-administration display prolonged adrenocortical activation and increased locomotor activity after exposure to the stress of novel environment (4-6). Glu cocorticoids promote activation and sensitization of the as cending dopaminergic neurons. Moreover, dopaminergic ac tivation of CRH neurons may occur (7,8). The data add to a growing body of evidence suggesting adverse effects of ab errant corticosteroid hormone signaling on dopaminedependent psychopathology; including psychoses precipi tated by excess glucocorticoids and stress. The susceptibility 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 ra t lines; 3) under basal morning conditions, apo-sus ra ts had significantly higher plasm a ACTH, but, in contrast, lower free cor ticosterone than apo-unsus rats; total plasm a 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 in creased ACTH level in apo-sus rats persisted into the afternoon 6 h postadrenalectomy; and 5) hippocampal mineralocorticoid (MR), but not glucocorticoid (GR), receptor capacity w as increased in apo-sus rats...

Reduced tumor growth, experimental metastasis formation, and angiogenesis in rats with a hyperreactive dopaminergic system

“…It is important to realize, however, that the differences between APO‐SUS and APO‐UNSUS rats are not limited to the dopaminergic system but also extend to other systems that interact with the dopaminergic system. For example, APO‐SUS rats show a large and long‐lasting endocrine response to stressors in terms of release of ACTH and corticosteroids, whereas APO‐UNSUS rats show small and short‐lasting endocrine responses to stress (32).…”

“…Like patients with schizophrenia, APO‐SUS rats are marked by an enhanced sensitivity to dopaminergic drugs such as amphetamine and apomorphine (24, 25, 29–31). Furthermore APO‐SUS rats and schizophrenic patients show a hyperreactive hypothalamus‐pituitary‐adrenal axis (32, 33). Most important, however, both APO‐SUS rats and patients with schizophrenia are characterized by an increased expression of tyrosine hydroxylase mRNA and an increased number of dopamine D2 receptors in the brain (34, 35).…”

The role of genetic and early environmental factors in determining apomorphine susceptibility

“…Thus both show an enhanced dopamine response (this paper; Rots et al 1996b), both show enhanced corticosterone release (Rots et al 1996a(Rots et al , 1996b, both show reduced prepulse inhibition (Ellenbroek et al , 1998, both show reduced latent inhibition , and both show an increase in tyrosine hydroxylase (Rots et al 1996b(Rots et al , 1996c. This suggests that APO-SUS mothers show less maternal behaviour than APO-UNSUS mothers, or that their maternal behaviour is of an inferior quality.…”

Basal and Stress‐Induced Differences in HPA Axis, 5‐HT Responsiveness, and Hippocampal Cell Proliferation in Two Mouse Lines

“…A difference in adrenocortical sensitivity to ACTH was also found in selection lines of rats. Rats genetically selected for low and high apomorphine susceptibility14,15 and Roman low‐ and high‐avoidance rats16 showed a similar difference in adrenocortical sensitivity to ACTH as the LAL and SAL mice. Moreover, LAL and SAL mice differ in apomorphine susceptibility and in avoidance behavior 3,6.…”