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 language | English |
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Pages (from-to) | 332-336 |
Number of pages | 5 |
Journal | Molecular Psychiatry |
Volume | 5 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Jan 2000 |
Externally published | Yes |
Keywords
- Atrial natriuretic factor producing neurons
- Dopamine receptor subtypes
- Glucocorticoid
- Primary neuron cultures