Oestradiol Modulation of Serotonin Reuptake Transporter and Serotonin Metabolism in the Brain of Monkeys

Serotonin (5‐hydroxytryptamine; 5‐ HT ) is an important brain neurotransmitter that is implicated in mental and neurodegenerative diseases and is modulated by ovarian hormones. Nevertheless, the effect of oestrogens on 5‐ HT neurotransmission in the primate caudate nucleus, putamen and nucleus accumbens, which are major components of the basal ganglia, and the anterior cerebral cortex, mainly the frontal and cingulate gyrus, is not well documented. The present study evaluated 5‐ HT reuptake transporter ( SERT ) and 5‐ HT metabolism in these brain regions in response to 1‐month treatment with 17β‐oestradiol in short‐term (1 month) ovariectomised ( OVX ) monkeys ( Macaca fascicularis ). SERT ‐specific binding was measured by autoradiography using the radioligand [ 3 H]citalopram. Biogenic amine concentrations were quantified by high‐performance liquid chromatography . 17β‐Oestradiol increased SERT in the superior frontal cortex and in the anterior cingulate cortex, in the nucleus accumbens, and in subregions of the caudate nucleus of OVX monkeys. 17β‐Oestradiol left [ 3 H]citalopram‐specific binding unchanged in the putamen, as well as the dorsal and medial raphe nucleus. 17β‐Oestradiol treatment decreased striatal concentrations of the precursor of 5‐ HT , 5‐hydroxytryptophan, and increased 5‐ HT , dopamine and 3‐methoxytyramine concentrations in the nucleus accumbens, caudate nucleus and putamen, whereas the concentrations of the metabolites 5‐hydroxyindoleacetic acid, 3,4‐dihydroxyphenylacetic acid and homovanillic acid remained unchanged. No effect of 17β‐oestradiol treatment was observed for biogenic amine concentrations in the cortical regions. A significant positive correlation was observed between [ 3 H]citalopram‐specific binding and 5‐ HT concentrations in the caudate nucleus, putamen and nucleus accumbens, suggesting their link. These results have translational value for women with low oestrogen, such as those in surgical menopause or perimenopause.