Dopamine, Reward Learning and Sex Hormones

Overview

Hormonal transition periods during the menstrual cycle may predispose women to mental disorders. Hormonal fluctuations provide specific neuroendocrine conditions that modulate brain structure and function and these actions affect cognitive and emotional behaviors and affect energy and mood homeostasis. It is thought that these changes are driven by altered dopamine transmission. Here, the investigators aim to examine (1) how sex hormones and dopamine are linked and also (2) how hormonal changes affect motivation, mood, and energy homeostasis. To this end, dopamine intervention will be tested on effort-based decision-making and motivational circuits in three hormonal stages (i.e., women in early-follicular phase (EF), women in mid-luteal phase (ML), and men). Additionally, the effects of hormonal status on metabolic indices will be tested, and its effects on mood fluctuations in a period of a month. The investigator hypothesizes that women in EF cycle phase (1) have naturally less dopamine and show less effort, and (2) they show greater improvement in effort-based decision-making after Levodopa administration. The investigator has exploratory outcomes about (3) sex differences in reward-learning with and without Levodopa administration and explores if these differences correlate with elevated female sex hormone levels. Moreover, it is hypothesized that (4) hormonal fluctuations affect energy homeostasis, thus women in their EF cycle phase have higher energy expenditure and (5) they report more negative mood than in their mid-luteal (ML) cycle phase.

This study will investigate naturally cycling women (n = 60) and men (n = 30). During the intake session (C1) energy expenditure of men and women in their EF cycle phase will be assessed by indirect calorimetry, participants will perform a training EAT task, and hormones (e.g., estradiol, progesterone, testosterone, and their precursor steroids and metabolites) will be assessed from blood samples. Energy expenditure will be assessed at another time point again (C2) (women with different hormonal profiles) and blood samples will be collected. During the neuroimaging sessions (S1, S2) both men and women will be measured, 30 women in their EF menstrual cycle phase and another 30 women in their ML phase. All participants will take part in the Effort Allocation Task, an effort-based decision-making task during an L-DOPA-based pharmaco-neuroimaging using functional magnetic resonance imaging (fMRI). To disentangle the influence of L-DOPA within a randomized double-blind design, in one session an L-DOPA-based pill (Madopar, 150mg/37.5 mg L-DOPA/ benserazide) and in another one a placebo pill will be administered. Sex steroids (e.g., progesterone, estrogen, testosterone) and metabolic hormones (e.g., glucose, insulin, triglyceride, ghrelin) will be obtained from blood samples. Before and after the MR scanning a reinforcement learning task will be examined. Over one month, a smartphone survey will be used to regularly record mood, premenstrual symptoms, and information on food cravings. Participants will be asked to start filling out the daily survey after C1 and continue it for 30 days.