title: Interaction between serotonin 5-HT1A receptors and beta-endorphins modulates antidepressant response.
abstract: Interactions between serotonergic and the endogenous opioid systems have been suggested to be involved in the etiopathogenesis of depression and in the mechanism of action of antidepressants. Activation of serotonin 5-HT1A receptors has been shown to increase plasma beta-endorphin (beta-END) levels in animal studies and in healthy humans.
  
  
  OBJECTIVE
  To assess interaction abnormalities between 5-HT1A receptors and the endogenous opioid system in patients with major depression and the possible modulating effect of citalopram.
  
  
  METHODS
  The beta-END response to the 5-HT1A receptor agonist, buspirone (30 mg), was measured in 30 patients with major depression and in 30 age- and sex-matched healthy controls before and after an 8-week treatment with citalopram. Pre-treatment score of the Hamilton Rating Scale for Depression (HRSD) was >or=17. Antidepressant response was defined by a 50% decrease in the HRSD. Pre- and post-treatment maximum peak response (Deltamax) and the area under the curve (AUC) of beta-END response were compared. Three time points were measured (60, 90 and 120 min). We also examined the correlations between the beta-END response and the antidepressant response. Buspirone plasma levels were not measured.
  
  
  RESULTS
  At baseline, beta-END response was similar in patients and controls. After 8 weeks of citalopram treatment depressed patients showed a significant decrease in the beta-END response (Deltamax: p<.001; AUC: p<.001). A significant correlation between the beta-END reduction in the response and the reduction in the HRSD score (r=.656; p<.001) was observed.
  
  
  CONCLUSIONS
  Changes in interaction between 5-HT1A receptor system and the endogenous opioid system may play a role both in the mechanism of action and response to antidepressant drugs.
authors: Institut de Neurociències, Hospital Clínic, Universitat de Barcelona, IDIBAPS, Barcelona, Spain. rnavines@hotmail.com
authors: Ricard
authors: R
authors: Navinés
authors: Rocío
authors: R
authors: Martín-Santos
authors: Esther
authors: E
authors: Gómez-Gil
authors: María J
authors: MJ
authors: Martínez de Osaba
authors: Cristòbal
authors: C
authors: Gastó
mesh_terms: D000293:Adolescent; D000328:Adult; D002065:Buspirone / Q000627:therapeutic use; D016022:Case-Control Studies; D015283:Citalopram / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D015592:Immunoradiometric Assay; D008297:Male; D008875:Middle Aged; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013997:Time Factors; D055815:Young Adult; D001615:beta-Endorphin / Q000097:blood*
chemical_list: D002065:Buspirone; D015283:Citalopram; D044282:Receptor, Serotonin, 5-HT1A; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D001615:beta-Endorphin