Interaction between serotonin 5-HT1A receptors and β-endorphins modulates antidepressant response

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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 β-endorphin (β-END) levels in animal studies and in healthy humans.


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.


The β-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 ≥ 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.


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.


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.

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