Dose-dependent effects of estrogen on prediction error related neural activity in the nucleus accumbens of healthy young women

TY - JOUR

T1 - Dose-dependent effects of estrogen on prediction error related neural activity in the nucleus accumbens of healthy young women

AU - Bayer, Janine

AU - Rusch, Tessa

AU - Zhang, Lei

AU - Gläscher, Jan

AU - Sommer, Tobias

PY - 2020/3

Y1 - 2020/3

N2 - RATIONALE: Whereas the effect of the sex steroid 17-beta-estradiol (E2) on dopaminergic (DA) transmission in the nucleus accumbens (NAc) is well evidenced in female rats, studies in humans are inconsistent. Moreover, linear and inverted u-shaped dose response curves have been observed for E2's effects on hippocampal plasticity, but the shape of dose response curves for E2's effects on the NAc is much less characterized.OBJECTIVES: Investigation of dose response curves for E2's effects on DA-related neural activity in the human NAc.METHODS: Placebo or E2 valerate in doses of 2, 4, 6 or 12 mg was orally administered to 125 naturally cycling young women during the low-hormone menstruation phase on two consecutive days using a randomized, double-blinded design. The E2 treatment regimen induced a wide range of E2 levels, from physiological (2- and 4-mg groups; equivalent to cycle peak) to supraphysiological levels (6- and 12-mg groups; equivalent to early pregnancy). This made it possible to study different dose response functions for E2's effects on NAc activity. During E2 peak, participants performed a well-established reversal learning paradigm. We used trial-wise prediction errors (PE) estimated via a computational reinforcement learning model as a proxy for dopaminergic activity. Linear and quadratic regression analyses predicting PE-related NAc activity from salivary E2 levels were calculated.RESULTS: There was a positive linear relationship between PE-associated NAc activity and salivary E2 increases.CONCLUSIONS: The randomized, placebo-controlled elevation of E2 levels stimulates NAc activity in the human brain, likely mediated by dopaminergic processes.

AB - RATIONALE: Whereas the effect of the sex steroid 17-beta-estradiol (E2) on dopaminergic (DA) transmission in the nucleus accumbens (NAc) is well evidenced in female rats, studies in humans are inconsistent. Moreover, linear and inverted u-shaped dose response curves have been observed for E2's effects on hippocampal plasticity, but the shape of dose response curves for E2's effects on the NAc is much less characterized.OBJECTIVES: Investigation of dose response curves for E2's effects on DA-related neural activity in the human NAc.METHODS: Placebo or E2 valerate in doses of 2, 4, 6 or 12 mg was orally administered to 125 naturally cycling young women during the low-hormone menstruation phase on two consecutive days using a randomized, double-blinded design. The E2 treatment regimen induced a wide range of E2 levels, from physiological (2- and 4-mg groups; equivalent to cycle peak) to supraphysiological levels (6- and 12-mg groups; equivalent to early pregnancy). This made it possible to study different dose response functions for E2's effects on NAc activity. During E2 peak, participants performed a well-established reversal learning paradigm. We used trial-wise prediction errors (PE) estimated via a computational reinforcement learning model as a proxy for dopaminergic activity. Linear and quadratic regression analyses predicting PE-related NAc activity from salivary E2 levels were calculated.RESULTS: There was a positive linear relationship between PE-associated NAc activity and salivary E2 increases.CONCLUSIONS: The randomized, placebo-controlled elevation of E2 levels stimulates NAc activity in the human brain, likely mediated by dopaminergic processes.

U2 - 10.1007/s00213-019-05409-7

DO - 10.1007/s00213-019-05409-7

M3 - SCORING: Journal article

C2 - 31773208

VL - 237

SP - 745

EP - 755

JO - PSYCHOPHARMACOLOGY

JF - PSYCHOPHARMACOLOGY

SN - 0033-3158

IS - 3

ER -