Dopamine, Reward Learning and Sex Hormones

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.

Eligibility Criteria:
Inclusion Criteria:

* Naturally cycling healthy women and men
* Age between 20-35
* Body-mass index (BMI): 18-28 kg/m2
* German or English language fluency
* Normal or corrected to normal vision
* For women: Regular menstrual cycle, no hormonal contraception (between 25 and 31 days)

Exclusion Criteria:

* Lifetime history of brain injury, stroke, epilepsy, seizures, schizophrenia, bipolar disorders, or severe alcohol/substance dependence, premenstrual dysphoric disorder (anamnestic survey)
* Mood disorder, anxiety disorder, obsessive-compulsive disorder, trauma- and stressor related disorder, somatic symptom disorder or eating disorder in the last 12 months prior to testing (anamnestic survey)
* Severe/uncontrolled medical problems such as hormonal, metabolic, heart or chronic diseases (e.g., severe hypertension, diabetes, dysfunctions of the thyroid, or congestive heart failure)
* Pregnancy, delivery, and lactation (current and within the last year; anamnestic survey)
* Undergoing regular hormonal treatment
* Daily smoking (nicotine, shisha, e-cigarettes) or \>1/week (cannabis)
* History of malignant melanoma, angle-closure glaucoma, gastrointestinal ulcers, and osteomalacia
* Hypersensitivity to: Microcrystalline cellulose, Mannitol (Ph.Eur.), Calcium hydrogen phosphate, Pregelatinized Starch (Corn), Crospovidone, Ethylcellulose, Fumed silica, Docusate sodium, Magnesium Stearate (Ph.Eur.), Iron/Ferric oxide (E 172)
* Taking certain types of medication (antihypertensive drugs, sympathomimetics, antipsychotics, drugs affecting the extrapyramidal motor system), non-selective MAO inhibitors or a combination of MAO-A and MAO-B inhibitors
* Since we will only include healthy participants, other medications that might contraindicate Levodopa (e.g., for mental disorders) will be excluded as well. Any other occasional medication will be evaluated on a case-by-case basis.
* Pathological hearing or increased sensitivity to loud noises
* Contraindication for MRI
* Claustrophobia
* Non-removable metal objects on or in the body
* Moderate or severe head injury