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5-HT1A receptor function in normal subjects on clinical doses of fluoxetine: blunted temperature and hormone responses to ipsapirone challenge.
Neuropsychopharmacology 1999; 20(6):628-39N

Abstract

Serotonergic receptors of the 5-HT1A 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-HT1A receptor function in 15 normal volunteers. Hypothermic and hormone responses to the 5-HT1A 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-HT1A receptor mediated effects. These findings confirm and extend previous observations in rodents and humans and indicate that both post-synaptic 5-HT1A receptors in the hypothalamus, which mediate hormone responses to 5-HT1A agonists, and pre-synaptic 5-HT1A 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-HT1A 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.

Authors+Show Affiliations

Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10327431

Citation

Lerer, B, et al. "5-HT1A Receptor Function in Normal Subjects On Clinical Doses of Fluoxetine: Blunted Temperature and Hormone Responses to Ipsapirone Challenge." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 20, no. 6, 1999, pp. 628-39.
Lerer B, Gelfin Y, Gorfine M, et al. 5-HT1A receptor function in normal subjects on clinical doses of fluoxetine: blunted temperature and hormone responses to ipsapirone challenge. Neuropsychopharmacology. 1999;20(6):628-39.
Lerer, B., Gelfin, Y., Gorfine, M., Allolio, B., Lesch, K. P., & Newman, M. E. (1999). 5-HT1A receptor function in normal subjects on clinical doses of fluoxetine: blunted temperature and hormone responses to ipsapirone challenge. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 20(6), pp. 628-39.
Lerer B, et al. 5-HT1A Receptor Function in Normal Subjects On Clinical Doses of Fluoxetine: Blunted Temperature and Hormone Responses to Ipsapirone Challenge. Neuropsychopharmacology. 1999;20(6):628-39. PubMed PMID: 10327431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-HT1A receptor function in normal subjects on clinical doses of fluoxetine: blunted temperature and hormone responses to ipsapirone challenge. AU - Lerer,B, AU - Gelfin,Y, AU - Gorfine,M, AU - Allolio,B, AU - Lesch,K P, AU - Newman,M E, PY - 1999/5/18/pubmed PY - 1999/5/18/medline PY - 1999/5/18/entrez SP - 628 EP - 39 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 20 IS - 6 N2 - Serotonergic receptors of the 5-HT1A 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-HT1A receptor function in 15 normal volunteers. Hypothermic and hormone responses to the 5-HT1A 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-HT1A receptor mediated effects. These findings confirm and extend previous observations in rodents and humans and indicate that both post-synaptic 5-HT1A receptors in the hypothalamus, which mediate hormone responses to 5-HT1A agonists, and pre-synaptic 5-HT1A 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-HT1A 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. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/10327431/5_HT1A_receptor_function_in_normal_subjects_on_clinical_doses_of_fluoxetine:_blunted_temperature_and_hormone_responses_to_ipsapirone_challenge_ L2 - http://dx.doi.org/10.1016/S0893-133X(98)00106-7 DB - PRIME DP - Unbound Medicine ER -