Journal
JOURNAL OF NEUROSCIENCE
Volume 21, Issue 10, Pages 3572-3579Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.21-10-03572.2001
Keywords
serotonin; ACTH; oxytocin; MDL 100,907; c-fos; Fos; prolactin; renin; corticosterone
Categories
Funding
- NIMH NIH HHS [R01 MH 58448, R01 MH058448] Funding Source: Medline
- NINDS NIH HHS [R01 NS034153, R01 NS 34153] Funding Source: Medline
Ask authors/readers for more resources
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 (+)-alpha-(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 congruent to 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available