Effects of 6-Hydroxydopamine on the Hypothalamo-Pituitary-Adrenocortical Axis

Abstract

Female rats were treated with two intraventricular injections each of 350 µg 6-hydroxydopamine (6-OHDA) and used for experiment 4 or 14 days later. The response to laparotomy, as assessed by subsequent in vitro corticosterone release, was unaffected by the drug, but that to the smaller stress of a skin cut was significantly reduced. Both fast and delayed feedback responses to corticosterone administration were still evident in 6-OHDA-treated animals. When determined 14 days after treatment, hypothalamic concentrations of epinephrine (E) and norepinephrine (NE) were reduced by 46 and 84%, respectively. There was no significant change in content of immunoreactive corticotropin-releasing factor (CRF-41). The acetylcholine-stimulated release of CRF bioactivity from control hypothalami incubated in vitro was significantly inhibited by E or NE, with E being at least 10 times more potent on a molar basis. This effect of NE was enhanced in hypothalami removed from 6-OHDA-treated rats, complete inhibition of acetylcholine-stimulated release of CRF being produced by 0.6 nMNE, as opposed to 6.0 nM for untreated controls. At the level of the anterior pituitary gland, tissue content of adrenocorticotropin (ACTH) was unaffected by treatment, but that of luteinizing hormone (LH) in the same tissues was significantly increased. The corticotrophic response of fragments of the gland incubated or perifused in vitro to hypothalamic extract, CRF-41, arginine vasopressin or E was reduced. In contrast, the response of the tissue to gonadotro-pin-releasing hormone (GnRH) added in vitro was not significantly affected. There was no difference in release of corticosterone from adrenals glands removed from control and 6-OHDA-treated rats and incubated in vitro, either basally or in response to synthetic ACTH 1–24. Treatment with 6-OHDA had no significant effect on adrenal gland weight or the compensatory adrenal hypertrophy seen 4 days after unilateral adrenalectomy.

Decreased Corticotropin‐Releasing Factor Receptor Expression and Adrenocorticotropic Hormone Responsiveness in Anterior Pituitary Cells of Wistar‐Kyoto Rats

“…There is a discordance between the hyperactive in vivo versus the blunted in vitro ACTH responsiveness to stress and to ACTH secretagogues in WKY rats. Similar discordance has been seen in rats after central 6‐hydroxidopamine administration in vivo (36) and in adrenalectomized rats. Adrenalectomy leads to elevated levels of ACTH secretion and POMC mRNA expression.…”

Recovery of the components of the hypothalamo-pituitary-adrenocortical axis in the rat after chronic treatment with prednisolone

“…At this time, however, the acetylcholine-induced release of CRF from the hypothalamus in vitro is still significantly reduced, implying that this single index overestimates the func¬ tional impairment of the tissue. There are several neurotransmitters implicated in the mediation of the stress response (Smelik, 1977;Nicholson, Holmes, Campbell et al 1986) and these results indicate that the degree of suppression by prednisolone of these systems overall is less prolonged than that of the acetylcholine response alone.…”

Central Mechanisms of Ethanol-Induced Adrenocortical Response in Selectively Bred Lines of Mice

“…However, the inherent pro blems associated with these pharmacological manipula tions may account for these discrepant results. For exam ple, postsynaptic receptor supersensitivity accompanies the decrease in central norepinephrine content approximately 10-14 days following treatment with 6-hydroxydopamine [24,40], Additionally, these manipulations are incapable of completely (i.e. >95%) depleting the functional reserves of intraneuronal catecholamines and, therefore, these systems may be marginally capable of maintaining normal noradre nergic tones [58].…”