A causal role for estradiol in human reinforcement learning

The sex hormone estrogen is hypothesized to play a key role in human cognition via its interactions with the dopaminergic system. Work in rodents has shown that estrogens most potent form, estradiol, impacts striatal dopamine functioning predominately via increased D1-receptor signalling, while human work has suggested that high estradiol levels are associated with altered reward sensitivity. Here, we addressed two fundamental questions: 1) whether estradiol causally alters reward sensitivity in men, and 2) whether this effect of estradiol is moderated by individual variation in polymorphisms of dopaminergic genes. To test this, we performed a double-blind placebo-controlled administration study in which hundred men received either a single dose of estradiol (2 mg) or placebo. We found that estradiol administration increased reward sensitivity, which was moderated by baseline dopamine. This was observed in choice behaviour and increased learning rates. These results confirm a causal role of estradiol in reinforcement learning in men that is moderated by the striatal dopaminergic pathway.