title: Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment.
abstract: BACKGROUND
  The serotonin-1A (5-HT1A) receptor subtypes are considered as targets of a variety of antidepressant drugs. Previous studies have suggested different adaptive changes in pre- and post-synaptic 5-HT receptors in the brain after treatment with non-selective tricyclic antidepressants (TCA) and selective 5-HT re-uptake inhibitors (SSRIs). The present study aimed to investigate the adaptive effect of the TCA imipramine on the post-synaptic 5-HT1A receptor function in the hypothalamus.
  
  
  METHODS
  A longitudinal design was used in 14 patients with major depressive disorder (DSM-IV) with endogenous features (Newcastle Scale) in order to assess the functional status of post-synaptic 5-HT1A receptors before and after successful antidepressant treatment with imipramine. The effect of the 5-HT1A receptor agonist, buspirone, on ACTH, cortisol, and prolactine (PRL) plasma levels was used to assess the functional status of hypothalamic 5-HT1A receptors. A group of 15 concurrent normal subjects were used as control.
  
  
  RESULTS
  Endogenous depressed patients in remission and currently receiving treatment with imipramine (mean length of treatment 145 days, SD=27) presented significantly lower buspirone responses to ACTH and cortisol than in the pre-treatment condition (Deltamax p< or =.05; AUC p<.001) and to ACTH in comparison with healthy controls (Deltamax p<.01; AUC p<.05). No significant differences were found between the post-treatment and pre-treatment PRL responses, or between patients in both conditions and controls; nevertheless, the PRL response in patients in remission and receiving treatment almost reached the values seen in controls.
  
  
  CONCLUSIONS
  This study extends previous findings from our group using the SSRI citalopram as an antidepressant. Imipramine and citalopram induce similar changes in the endocrine response to buspirone in depressed patients. As the direction of change in ACTH-cortisol and PRL responses after treatment is the opposite, we cannot substantiate increases or decreases in the sensitivity of post-synaptic 5-HT1A receptors in the hypothalamus by long-term imipramine treatment and/or resolution of illness. Therefore, the hormonal changes may result from different or multiples unknown mechanisms.
authors.affiliation: Servicio de Psiquiatría, Instituto de Neurociencias, Hospital Clínic, Instituto de Investigaciones Biomédiques August Pi i Sunyer (IDIBAPS), Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain. esgomez@clinic.ub.es
authors.forename: Esther
authors.initials: E
authors.lastname: Gómez-Gil
authors.forename: Ricard
authors.initials: R
authors.lastname: Navinés
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Martínez De Osaba
authors.forename: Maribel
authors.initials: M
authors.lastname: Díaz-Ricart
authors.forename: Ginés
authors.initials: G
authors.lastname: Escolar
authors.forename: Manel
authors.initials: M
authors.lastname: Salamero
authors.forename: Rocío
authors.initials: R
authors.lastname: Martín-Santos
authors.forename: Ana
authors.initials: A
authors.lastname: Galán
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Gastó
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage; D002065:Buspirone / Q000494:pharmacology*; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology / Q000534:rehabilitation; D003940:Diagnostic Techniques, Endocrine; D004334:Drug Administration Schedule; D005260:Female; D006728:Hormones / Q000097:blood* / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D007099:Imipramine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D012074:Remission Induction; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D006728:Hormones; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007099:Imipramine; D002065:Buspirone; D006854:Hydrocortisone