Background: Progesterone (P) is thought to influence mood and affective states. Alterations of the inhibitory serotonin-1A (5-HT1A) receptor distribution are associated with depression and anxiety. This study evaluates the influence of plasma P levels on the 5-HT1A receptor binding in healthy male subjects. Methods: Molecular neuroimaging of the 5-HT1A receptor distribution using positron emission tomography and hormone assays for total plasma P and cortisol were done in a sample of 18 healthy men. Results: Plasma P levels explained up to 65% of the variability in 5-HT1A receptor binding in limbic regions including the amygdala, orbitofrontal cortex and retrosplenial cortex. When controlling for cortisol in the model, there was an expected decline in explained variances of 5-HT1A binding attributed to P. Conclusions: The results of this study provide further support for the effect of P on 5-HT1A receptor expression and raise the possibility that P mediates the vulnerability to mood disorders by affecting the serotonergic system.

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