Glucocorticoid modulation of dopamine mediated effects on hypothalamic atrial natriuretic faster neurons

D. Lee, W. Huang, L. Wang, D. Copolov, A. T. Lim

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Dopamine (DA) plays an important role in cognition, neuroendocrine functions and psychosis. Whilst stress adversely affects some of these functions, its neurobiological basis remains unclear. In the rat hypothalamus, a concurrent activation of D5 and D2 receptors by dopamine produces a biphasic effect on the function of atrial natriuretic factor (ANF) neurons. Whereas low doses (10-8 and 10-7 M) of DA suppress the release and pro-ANF mRNA expression, high doses (10-6 and 10-5 M) of the amine produce an opposite effect through the interaction of D5 and D2 receptors. We report here that the augmenting effect of DA on the hypothalamic neurons is inhibited by a synthetic glucocorticoid, dexamethasone (DM), in both time-dependent and dose-related manner with an EC50 of 0.1 nM. Furthermore, the inhibition is blocked by 100 nM of RU38486 (P < 0.01), a glucocorticoid receptor antagonist, but not by an equivalent dose of RU28318, a mineralocorticoid receptor antagonist. In contrast, DM failed to modulate low doses (10-8 to 10-7 M) of DA-induced suppression of ir-ANF release and pro-ANF mRNA expression that was mediated primarily through D2 receptors. We conclude that glucocorticoids markedly alter DA-induced biphasic effects by down-regulating D5, but not D2, receptor-mediated neurobiological events. Hence, in severe stress, high levels of circulating glucocorticoids may render dopamine to act as a potent suppressor of neurons that possess both D5 and D2 receptors. The possibility that this novel mechanism of stress hormone or glucocorticoids may, in part, undermine DA-mediated neurophysiology in critical regions of the brain, which links to psychosis now needs to be considered.

Original languageEnglish
Pages (from-to)332-336
Number of pages5
JournalMolecular Psychiatry
Volume5
Issue number3
DOIs
Publication statusPublished - 1 Jan 2000
Externally publishedYes

Keywords

  • Atrial natriuretic factor producing neurons
  • Dopamine receptor subtypes
  • Glucocorticoid
  • Primary neuron cultures

Cite this

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title = "Glucocorticoid modulation of dopamine mediated effects on hypothalamic atrial natriuretic faster neurons",
abstract = "Dopamine (DA) plays an important role in cognition, neuroendocrine functions and psychosis. Whilst stress adversely affects some of these functions, its neurobiological basis remains unclear. In the rat hypothalamus, a concurrent activation of D5 and D2 receptors by dopamine produces a biphasic effect on the function of atrial natriuretic factor (ANF) neurons. Whereas low doses (10-8 and 10-7 M) of DA suppress the release and pro-ANF mRNA expression, high doses (10-6 and 10-5 M) of the amine produce an opposite effect through the interaction of D5 and D2 receptors. We report here that the augmenting effect of DA on the hypothalamic neurons is inhibited by a synthetic glucocorticoid, dexamethasone (DM), in both time-dependent and dose-related manner with an EC50 of 0.1 nM. Furthermore, the inhibition is blocked by 100 nM of RU38486 (P < 0.01), a glucocorticoid receptor antagonist, but not by an equivalent dose of RU28318, a mineralocorticoid receptor antagonist. In contrast, DM failed to modulate low doses (10-8 to 10-7 M) of DA-induced suppression of ir-ANF release and pro-ANF mRNA expression that was mediated primarily through D2 receptors. We conclude that glucocorticoids markedly alter DA-induced biphasic effects by down-regulating D5, but not D2, receptor-mediated neurobiological events. Hence, in severe stress, high levels of circulating glucocorticoids may render dopamine to act as a potent suppressor of neurons that possess both D5 and D2 receptors. The possibility that this novel mechanism of stress hormone or glucocorticoids may, in part, undermine DA-mediated neurophysiology in critical regions of the brain, which links to psychosis now needs to be considered.",
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Glucocorticoid modulation of dopamine mediated effects on hypothalamic atrial natriuretic faster neurons. / Lee, D.; Huang, W.; Wang, L.; Copolov, D.; Lim, A. T.

In: Molecular Psychiatry, Vol. 5, No. 3, 01.01.2000, p. 332-336.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Lee, D.

AU - Huang, W.

AU - Wang, L.

AU - Copolov, D.

AU - Lim, A. T.

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