Summary: A new study shows that estrogen naturally modulates dopamine signaling in the brain, altering how female rats learn reward cues across the reproductive cycle. When estrogen levels were high, dopamine responses in the reward center intensified, improving learning.
When estrogen signaling was suppressed, reward learning weakened, revealing a direct biological link between hormones and cognitive function. These findings may help explain why many neuropsychiatric symptoms fluctuate with hormonal changes and point to new paths for understanding hormone-linked disorders.
Key Facts
- Estrogen Boosts Learning: Higher estrogen levels amplified dopamine reward signals, enhancing learning performance.
- Cycle-Linked Fluctuations: Learning efficiency rose and fell with natural hormonal shifts across the reproductive cycle.
- Specific to Reward Learning: Estrogen influenced learning but did not affect decision-making abilities.
Source: NYU
Researchers have long established that hormones significantly affect the brain, creating changes in emotion, energy levels, and decision-making. However, the intricacies of these processes are not well understood.
A new study by a team of scientists focusing on the female hormone estrogen further illuminates the nature of these processes. In a series of experiments with laboratory rats, it finds that the neurological mechanisms underlying learning and decision-making naturally fluctuate over the female reproductive cycle due to previously undetected molecular changes related to dopamine, which broadcasts the “reward” signals that guide learning throughout 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.
The study, which also included researchers from NYU Grossman School of Medicine’s Neuroscience Institute and Virginia Commonwealth University’s Department of Pharmacology and Toxicology, examined the neurological activity of laboratory rats in response to a series of 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.
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.
Funding: 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Key Questions Answered:
A: Estrogen strengthens dopamine-based reward signals, boosting learning performance.
A: Molecular shifts linked to estrogen alter dopamine activity, changing how efficiently reward cues are learned.
A: Hormone–dopamine interactions may help explain why psychiatric symptoms vary with hormonal states.
About this dopamine, estrogen, and learning research news
Author: James Devitt
Source: NYU
Contact: James Devitt – NYU
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Estrogen modulates reward prediction errors and reinforcement learning” by Christine Constantinople et al. Nature Neuroscience
Abstract
Estrogen modulates reward prediction errors and reinforcement learning
Gonadal hormones act throughout the brain and modulate psychiatric symptoms. Yet how hormones influence cognitive processes is unclear.
Exogenous 17β-estradiol, the most potent estrogen, modulates dopamine in the nucleus accumbens core, which instantiates reward prediction errors (RPEs), the difference between received and expected reward.
Here we show that following endogenous increases in 17β-estradiol, dopamine RPEs and behavioral sensitivity to previous rewards are enhanced, and nucleus accumbens core dopamine reuptake proteins are reduced. Rats adjusted how quickly they initiated trials in a task with varying reward states, balancing effort against expected rewards.
Nucleus accumbens core dopamine reflected RPEs that influenced rats’ initiation times. Higher 17β-estradiol predicted greater sensitivity to reward states and larger RPEs. Proteomics revealed reduced dopamine transporter expression following 17β-estradiol increases. Finally, knockdown of midbrain estrogen receptors suppressed sensitivity to reward states.
Therefore, endogenous 17β-estradiol predicts dopamine reuptake and RPE signaling, and causally dictates the impact of previous rewards on behavior.
