5-HT2A Receptors Stimulate ACTH, Corticosterone, Oxytocin, Renin, and Prolactin Release and Activate Hypothalamic CRF and Oxytocin-Expressing Cells
Louis D. van de Kar, Adil Javed, Ya-Hong Zhang, F. Serres, D. Raap, T. S. Gray
Journal of Neuroscience May 15, 2001 DOI: 10.1523/jneurosci.21-10-03572.2001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical pharmacological study in rats Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | DOI MDL 100 907 |
| Dose | DOI 2.5 mg/kg i.p.; MDL 100,907 0.001, 0.01, or 0.1 mg/kg s.c. |
| Measures | plasma levels of ACTH, corticosterone, oxytocin, prolactin, and renin; Fos immunoreactivity |
| Topics | Serotonin |
| Key points | The 5-HT2A antagonist MDL 100,907 dose-dependently blocked DOI-induced increases in ACTH, corticosterone, oxytocin, prolactin, and renin, with complete blockade at 0.01–0.1 mg/kg. MDL 100,907 also blocked DOI-induced Fos expression in hypothalamic CRF and oxytocin neurons and in the amygdala, bed nucleus of the stria terminalis, and prefrontal cortex. The authors suggest that DOI's neuroendocrine effects are mediated by 5-HT2A receptor activation of hypothalamic paraventricular nucleus neurons and associated circuitry. |
Abstract
The 5-HT2A/2C agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) stimulates hypothalamic neurons to increase the secretion of several hormones. This study addressed two questions: 1) are the neuroendocrine effects of DOI mediated via activation of 5-HT2A receptors; and 2) which neurons are activated by 5-HT2A receptors. The 5-HT2A antagonist (+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (MDL 100,907; 0.001, 0.01, or 0.1 mg/kg, s.c.) was administered before rats were challenged with DOI (2.5 mg/kg, i.p.). MDL 100,907 produced a dose-dependent inhibition (ED50 ≅ 0.001 mg/kg) of the effect of DOI on plasma levels of ACTH, corticosterone, oxytocin, prolactin, and renin without altering basal hormone levels. Complete blockade of the effect of DOI was achieved for all hormones at MDL 100,907 doses of 0.01–0.1 mg/kg. In a parallel experiment, DOI was injected 2 hr before killing to determine its effects on the expression of Fos, the product of the immediate early gene c-fos. DOI induced an increase in Fos immunoreactivity in corticotropin-releasing factor (CRF) and in oxytocin-expressing neurons but not in vasopressin-containing neurons in the hypothalamic paraventricular nucleus or CRF cells in the amygdala. Pretreatment with MDL 100,907 (0.1 mg/kg, s.c.) blocked the DOI-induced increase in Fos expression in all regions including the hypothalamus, amygdala (central and corticomedial), bed nucleus of the stria terminalis, and prefrontal cortical regions. The combined neuroanatomical and pharmacological observations suggest that the neuroendocrine responses to DOI are mediated by activation of neurons in the hypothalamic paraventricular nucleus and associated circuitry. Furthermore, selective activation of 5-HT2A receptors mediates the hormonal and Fos-inducing effects of DOI.
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