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-HT_1A receptors has been shown to increase plasma β-endorphin (β-END) levels in animal studies and in healthy humans.

Objectives

To assess interaction abnormalities between 5-HT_1A receptors and the endogenous opioid system in patients with major depression and the possible modulating effect of citalopram.

Methods

The β-END response to the 5-HT_1A 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 ≥ 17. Antidepressant response was defined by a 50% decrease in the HRSD. Pre- and post-treatment maximum peak response (Δmax) and the area under the curve (AUC) of β-END response were compared. Three time points were measured (60, 90 and 120 min). We also examined the correlations between the β-END response and the antidepressant response. Buspirone plasma levels were not measured.

Results

At baseline, β-END response was similar in patients and controls. After 8 weeks of citalopram treatment depressed patients showed a significant decrease in the β-END response (Δmax: p < .001; AUC: p < .001). A significant correlation between the β-END reduction in the response and the reduction in the HRSD score (r = .656; p < .001) was observed.

Conclusions

Changes in interaction between 5-HT_1A receptor system and the endogenous opioid system may play a role both in the mechanism of action and response to antidepressant drugs.