TY - JOUR
T1 - 5-HT(1A) Receptor function in normal subjects on clinical doses of fluoxetine
T2 - Blunted temperature and hormone responses to ipsapirone challenge
AU - Lerer, Bernard
AU - Gelfin, Yevgenia
AU - Gorfine, Malka
AU - Allolio, Bruno
AU - Lesch, K. Peter
AU - Newman, Michael E.
PY - 1999/6
Y1 - 1999/6
N2 - Serotonergic receptors of the 5-HT(1A) subtype have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, including specific serotonin reuptake inhibitors (SSRIs). We examined the effect of clinical doses of the SSRI, fluoxetine, on 5-HT(1A) receptor function in 15 normal volunteers. Hypothermic and hormone responses to the 5-HT(1A) receptor agonist, ipsapirone (0.3 mg per kg, per os) were examined after two weeks of placebo and again, after the subjects had been receiving fluoxetine for four weeks. On fluoxetine, the hypothermic response to ipsapirone was significantly blunted, as were ACTH, cortisol and growth hormone release. Ipsapirone plasma levels were significantly increased by fluoxetine but a pharmacokinetic effect could not have accounted for the observed blunting of 5-HT(1A) receptor mediated effects. These findings confirm and extend previous observations in rodents and humans and indicate that both post-synaptic 5-HT(1A) receptors in the hypothalamus, which mediate hormone responses to 5-HT(1A) agonists, and pre-synaptic 5-HT(1A) receptors which (putatively) mediate the hypothermic response, are rendered subsensitive by chronic SSRI administration. Since fluoxetine did not have significant effects on mood and other psychological variables in these subjects, alterations in 5-HT(1A) receptor function induced by SSRIs may have psychotropic relevance only in the context of existing perturbations of serotonergic function which underlie the psychopathological states in which these drugs are therapeutically effective. Copyright (C) 1999 American College of Neuropsychopharmacology.
AB - Serotonergic receptors of the 5-HT(1A) subtype have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, including specific serotonin reuptake inhibitors (SSRIs). We examined the effect of clinical doses of the SSRI, fluoxetine, on 5-HT(1A) receptor function in 15 normal volunteers. Hypothermic and hormone responses to the 5-HT(1A) receptor agonist, ipsapirone (0.3 mg per kg, per os) were examined after two weeks of placebo and again, after the subjects had been receiving fluoxetine for four weeks. On fluoxetine, the hypothermic response to ipsapirone was significantly blunted, as were ACTH, cortisol and growth hormone release. Ipsapirone plasma levels were significantly increased by fluoxetine but a pharmacokinetic effect could not have accounted for the observed blunting of 5-HT(1A) receptor mediated effects. These findings confirm and extend previous observations in rodents and humans and indicate that both post-synaptic 5-HT(1A) receptors in the hypothalamus, which mediate hormone responses to 5-HT(1A) agonists, and pre-synaptic 5-HT(1A) receptors which (putatively) mediate the hypothermic response, are rendered subsensitive by chronic SSRI administration. Since fluoxetine did not have significant effects on mood and other psychological variables in these subjects, alterations in 5-HT(1A) receptor function induced by SSRIs may have psychotropic relevance only in the context of existing perturbations of serotonergic function which underlie the psychopathological states in which these drugs are therapeutically effective. Copyright (C) 1999 American College of Neuropsychopharmacology.
KW - 5-HT(1A) receptors
KW - ACTH
KW - Cortisol
KW - Fluoxetine
KW - Growth hormone
KW - Ipsapirone
KW - Specific serotonin reuptake inhibitors (SSRIs)
UR - http://www.scopus.com/inward/record.url?scp=0033137334&partnerID=8YFLogxK
U2 - 10.1016/S0893-133X(98)00106-7
DO - 10.1016/S0893-133X(98)00106-7
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C2 - 10327431
AN - SCOPUS:0033137334
SN - 0893-133X
VL - 20
SP - 628
EP - 639
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 6
ER -