Evidence of the dopamine-2 receptor mediated inhibition of the hypothalamic-pituitary-adrenal system; a rodent model of hypercortisolism in chronic neuropsychiatric disorders

Abstract

The purpose of this study was to examine the role of dopaminergic mediation in the hypothalamic-pituitary-adrenal (HPA) response challenged by ether stress. First the effects of the D1 selective (SCH-23390) and the D2 selective (haloperidol) dopamine antagonists on ether stress evoked corticosterone responses were tested. The activation of the HPA axis was assessed by measuring plasma corticosterone levels. Low doses of haloperidol (25 nmol/kg, intraperitoneally) failed to affect either basal or stimulated corticosterone secretion, while SCH-23390 elicited moderate inhibition of stimulated release. However, to our surprise higher doses of haloperidol (250 nmol/kg) raised basal secretion and even potentiated the HPA response evoked by ether stress. Therefore to elucidate the role of D 2 mediation, the intrinsic activity of the D 2 antagonist was tested in further experiments. Haloperidol (from 25 nmol/kg to 2.5 mmol/kg) alone elicited a dose-dependent activation of the HPA system reflected by both corticosterone and ACTH serum levels. This D 2 -antagonist-evoked HPA activation could be prevented by pre-administration of the CRH antagonist, α-helical CRH 9-41 . These findings provide unequivocal evidence that D 2 receptor can exert inhibitory control over the HPA axis.

Intravenous haloperidol and cocaine alter the distribution of T CD3+CD4+, non‐T/NK and NKT cells in rats

“…Cocaine activates the HPA axis, 41 one of the major pathways through which cocaine modulates the immune system 24,25 . Haloperidol has bidirectional effects on the HPA axis, depending on the dose and route of administration: there is a tendency to increase the release of ‘stress hormones’ at higher doses and routes, which provides a more rapid delivery of the drug to the brain 42–45 . HPA axis activation is commonly associated with lymphopenia and immunosuppression 46 .…”

“…24,25 Haloperidol has bidirectional effects on the HPA axis, depending on the dose and route of administration: there is a tendency to increase the release of 'stress hormones' at higher doses and routes, which provides a more rapid delivery of the drug to the brain. [42][43][44][45] HPA axis activation is commonly associated with lymphopenia and immunosuppression. 46 In our study, intravenous infusions of haloperidol and cocaine resulted in an increased concentration of plasma corticosterone, accompanied by pronounced lymphopenia.…”