Experiments reveal how estrogen enhances dopamine and cognitive function.
Hormones are known to have powerful effects on the brain, influencing mood, motivation, and decision-making. Yet, the precise biological mechanisms behind these effects remain only partially understood.
A new investigation centered on the female hormone estrogen offers deeper insight into these complex processes. Through a series of experiments in laboratory rats, the research team discovered that the brain’s learning and decision-making systems shift naturally across the female reproductive cycle. These changes are driven by previously unseen molecular variations connected to dopamine, the neurotransmitter responsible for sending “reward” signals that guide learning across the brain.
The work is reported in the journal Nature Neuroscience.
“Despite the broad influence of hormones throughout the brain, little is known about how these hormones influence cognitive behaviors and related neurological activity,” says Christine Constantinople, a professor in New York University’s Center for Neural Science and the paper’s senior author. “There is a growing realization in the medical community that changes in estrogen levels are related to cognitive function and, specifically, psychiatric disorders.”
“Our results provide a potential biological explanation that bridges dopamine’s function with learning in ways that better inform our understanding of both health and disease,” adds Carla Golden, an NYU postdoctoral fellow and the paper’s lead author.
Laboratory experiments link estrogen to learning performance
The study, conducted in collaboration with researchers from NYU Grossman School of Medicine’s Neuroscience Institute and Virginia Commonwealth University’s Department of Pharmacology and Toxicology, analyzed patterns of neurological activity in laboratory rats during a set of behavioral experiments.
In them, the rodents successfully reached a “reward”—in this case, a water source—after learning the significance of audio cues, which signaled the water’s availability and volume.
Overall, the rats’ learning capabilities were enhanced when estrogen levels were increased. This happens, the authors write, because estrogen boosts dopamine activity in the brain’s reward center, making reward signals stronger.
Hormonal changes reveal a link to neuropsychiatric disorders
By contrast, when estrogen activity was suppressed, curbing its ability to regulate dopamine, learning capabilities were diminished—and pointed to a potential connection between hormone levels and symptoms of neuropsychiatric disorders. Importantly, the researchers note, cognitive decision making was not affected by estrogen activity—the effect was specific to learning.
“All neuropsychiatric disorders show fluctuations in symptom severity over hormonal states, suggesting that a better understanding of how hormones influence neural circuits might reveal what causes these diseases,” observes Constantinople.
Reference: “Estrogen modulates reward prediction errors and reinforcement learning” by Carla E. M. Golden, Audrey C. Martin, Daljit Kaur, Andrew Mah, Diana H. Levy, Takashi Yamaguchi, Amy W. Lasek, Dayu Lin, Chiye Aoki and Christine M. Constantinople, 11 November 2025, Nature Neuroscience.
DOI: 10.1038/s41593-025-02104-z
This work was supported by grants from the National Institutes of Health (DP2MH126376, F32MH125448, 5T32MH019524, 1S10OD010582-01A1), the National Cancer Institute (P30CA016087), NYU Langone Health, and the Simons Foundation.
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