Interaction between serotonin 5-HT1A receptors and beta-endorphins modulates antidepressant response.
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.
Navinés
Ricard
R
Institut de Neurociències, Hospital Clínic, Universitat de Barcelona, IDIBAPS, Barcelona, Spain. rnavines@hotmail.com
Martín-Santos
Rocío
R
Gómez-Gil
Esther
E
Martínez de Osaba
María J
MJ
Gastó
Cristòbal
C
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*
D002065:Buspirone; D015283:Citalopram; D044282:Receptor, Serotonin, 5-HT1A; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D001615:beta-Endorphin