Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis: interaction between 5-HT1A and 5-HT2A receptors
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Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis : interaction between 5-HT1A and 5-HT2A receptors. / Mikkelsen, Jens D; Hay-Schmidt, Anders; Kiss, Alexander.
In: Annals of the New York Academy of Sciences, Vol. 1018, 06.2004, p. 65-70.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis
T2 - interaction between 5-HT1A and 5-HT2A receptors
AU - Mikkelsen, Jens D
AU - Hay-Schmidt, Anders
AU - Kiss, Alexander
PY - 2004/6
Y1 - 2004/6
N2 - Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these receptor subtypes are central to mediating the effects of SSRIs. To study the interaction of these receptors, rats were administered with the 5-HT(1A/7) agonist 8-OH-DPAT (0.05 to 1.25 mg/kg), the 5-HT(2A/C) agonist DOI (0.25 to 5 mg/kg), or a mixture of both compounds, and trunk blood was taken 60 min later. The two compounds given in combination produced a lower increase in corticosterone than DOI does alone. DOI and 8-OH-DPAT also produced a marked induction of c-Fos in the paraventricular nucleus (PVN), but the induction was not different if the two compounds were given together. These data show that the two serotonin receptor subtypes affect the HPA axis via a central target. In conclusion, 5-HT(1A) and 5-HT(2A) receptors regulate corticotrophin-releasing hormone (CRH) neurons via distinct but strongly interacting pathways, probably converging on the same neurons in the hypothalamus.
AB - Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these receptor subtypes are central to mediating the effects of SSRIs. To study the interaction of these receptors, rats were administered with the 5-HT(1A/7) agonist 8-OH-DPAT (0.05 to 1.25 mg/kg), the 5-HT(2A/C) agonist DOI (0.25 to 5 mg/kg), or a mixture of both compounds, and trunk blood was taken 60 min later. The two compounds given in combination produced a lower increase in corticosterone than DOI does alone. DOI and 8-OH-DPAT also produced a marked induction of c-Fos in the paraventricular nucleus (PVN), but the induction was not different if the two compounds were given together. These data show that the two serotonin receptor subtypes affect the HPA axis via a central target. In conclusion, 5-HT(1A) and 5-HT(2A) receptors regulate corticotrophin-releasing hormone (CRH) neurons via distinct but strongly interacting pathways, probably converging on the same neurons in the hypothalamus.
KW - 8-Hydroxy-2-(di-n-propylamino)tetralin
KW - Amphetamines
KW - Animals
KW - Dose-Response Relationship, Drug
KW - Hypothalamo-Hypophyseal System
KW - Male
KW - Pituitary-Adrenal System
KW - Rats
KW - Rats, Wistar
KW - Receptor, Serotonin, 5-HT1A
KW - Receptor, Serotonin, 5-HT2A
KW - Serotonin
KW - Serotonin 5-HT1 Receptor Agonists
KW - Serotonin 5-HT2 Receptor Agonists
KW - Serotonin Receptor Agonists
KW - Serotonin Uptake Inhibitors
U2 - 10.1196/annals.1296.007
DO - 10.1196/annals.1296.007
M3 - Journal article
C2 - 15240353
VL - 1018
SP - 65
EP - 70
JO - Annals of The Lyceum of Natural History of New York
JF - Annals of The Lyceum of Natural History of New York
SN - 0077-8923
ER -
ID: 47928649