Original Article

Neuropsychopharmacology (1999) 20, 628–639. doi:10.1016/S0893-133X(98)00106-7

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine: Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Bernard Lerer MD1, Yevgenia Gelfin MD1, Malka Gorfine MA2, Bruno Allolio MD3, K Peter Lesch MD4 and Michael E Newman Ph.D1

  1. 1Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  2. 2Laboratory of Applied Statistics, Hebrew University, Jerusalem, Israel
  3. 3Endocrine Laboratory, Department of Medicine, University of Wuerzburg, Wuerzburg, Germany
  4. 4Department of Psychiatry, University of Wuerzburg, Wuerzburg, Germany

Correspondence: Prof. Bernard Lerer, Biological Psychiatry Laboratory, Dept. of Psychiatry, Hadassah-Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel

Received 15 May 1998; Accepted 25 August 1998



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.


Fluoxetine; Specific serotonin reuptake inhibitors (SSRIs); 5-HT1A receptors; Ipsapirone; ACTH; Cortisol; Growth hormone

Extra navigation