Oxytocin is a hypothalamic neuropeptide that is best known for its peripheral physiological effects in the female organism i.e., uterine contractions during birth. The neuropeptide furthermore affects reward processing and metabolic functions such as eating behavior and body weight. Oxytocin receptors are present in brain regions associated with the processing of rewards, e.g., ventral tegmental area (VTA), nucleus accumbens (NAcc) and nucleus stria terminalis. Previous studies indicate that oxytocin interacts with sex hormones such as estradiol in a sex-specific manner. Despite known sex differences in oxytocin function, most studies i.e., on the metabolic effects of oxytocin in humans have so far focused on young, healthy men. Intranasal oxytocin administration has emerged as a method to experimentally investigate central nervous effects of oxytocin in the absence of relevant side effects. In the proposed study the investigators aim to systematically investigate the acute effect of intranasal oxytocin on reward processing in relation to circulating and synthetic sex hormones in healthy, naturally cycling women and in women taking hormonal oral contraceptive pills. The investigators will administer 24 international units (IU) of intranasal oxytocin vs. placebo and investigate neural correlates in a 3T MRI scanner including functional imaging during a reward processing task, changes in brain anatomy and connectivity. Additionally, metabolic functions, eating behavior and changes in mood and wellbeing will be assessed and blood will be drawn to assess parameters of hormonal and metabolic status.
This pharmaco-neuroimaging study will investigate four groups of women: (1) naturally cycling (NC) women in the follicular phase of the menstrual cycle (n = 25), (2) NC women in the luteal phase of the menstrual cycle (n = 25), (3) women taking combined oral hormonal contraceptives (OC) (n = 25), (4) women taking progestogen-only OC (n = 25). All participants will take part in an intake session (T0) and two experimental sessions (T1 and T2) scheduled approximately four weeks apart. In the intake session (T0) the eligibility of the participants i.e., MRI compatibility, will be verified. Additionally, the participants will be asked to fill out questionnaires i.e., regarding their personality, sleep and eating behavior and perform standardized cognitive tests. To disentangle the influence of oxytocin on reward processing and metabolism across different hormonal status in females, intranasal oxytocin (24 IU) will be administered in one experimental session and placebo in another, in a randomized and double-blind study design. The investigators will obtain sex steroids (e.g., progesterone, estrogen, testosterone) i.e., to verify the menstrual cycle phase, synthetic steroids (e.g., ethinylestradiol, levonorgestrel) and metabolic hormones (e.g., glucose, insulin, c-peptide) from blood samples in the two experimental sessions. In the baseline phase of each experimental session (T1 and T2), the investigators will assess the participants body composition with bioimpedance analysis and resting energy expenditure with indirect calorimetry. After the intranasal administration of oxytocin or placebo, a 3 Tesla (3T) functional magnetic resonance imaging (fMRI) session will follow including the Effort Allocation Task (EAT), an effort-based decision-making task, a resting-state fMRI and diffusion tensor imaging (DTI) scan. The experimental sessions will furthermore assess the participants mood, thirst and hunger throughout the experimental period and include a snack test to assess eating related behavior. Additionally, participants will be asked to fill out questionnaires assessing i.e., sleep, emotion regulation, decision making, sexual function and wellbeing. The investigators hypothesize that, (1) the acute effect of oxytocin on reward processing in naturally cycling women is most pronounced during the follicular phase and (2) the acute effect of oxytocin on reward processing in women is dampened by the intake of oral contraceptive pills (OCs), in particular progestogen-only pills.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
100
24 international units (IU) of Syntocinon, nasal spray solution; 1 ml nasal spray contains 40 I.U. oxytocin (equivalent to 67 mcg). One spray hub (0.1 ml) contains 4 I.U. oxytocin (equivalent to 6.7 mcg).
Nasal spray solution; Placebo will be administered as the placebo controlled condition.
University of Tuebingen; Department of Psychiatry & Psychotherapy; Institute of Medical Psychology and Behavioural Neurobiology
Tübingen, Baden-Wurttemberg, Germany
RECRUITINGOxytocin and sex hormone level induced changes in reward-related brain responses in the reward circuitry during effort-based decision making.
Comparing brain activity (BOLD signals) in the reward circuitry (ROIs: nucleus accumbens, putamen, caudate, ventral tegmental area, amygdala, ventromedial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula) and cognitive control areas (ROIs: dorsolateral and ventromedial prefrontal cortex, anterior cingulate cortex, supplementary motor area) of female participants in luteal menstrual cycle phase, follicular menstrual cycle phase, with combined OC intake and progestogen-only OC intake during a reward task with oxytocin vs placebo.
Time frame: During neuroimaging (60 minutes) oxytocin compared to placebo condition.
Oxytocin induced changes in reward related behavior.
Force exerted on grip force controller to obtain rewards and changes in behavioral parameters measured during the Effort Allocation Task after oxytocin vs. placebo administration.
Time frame: During neuroimaging (60 minutes) oxytocin compared to placebo condition.
Oxytocin induced changes in eating behaviour.
Number of consumed calories (kcal) in a snack test and subjective satiety in oxytocin vs. placebo condition.
Time frame: During the experimental session (approximately 4.5 hours).
Oxytocin induced changes in functional connectivity.
Functional connectivity of regions of the mesocorticolimbic circuitry (ROIs: nucleus accumbens, putamen, caudata, ventral tegmental area, amygdala, ventral medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) and limbic circuity (ROIs: hypothalamus, hippocampus) after oxytocin vs. placebo administration.
Time frame: During neuroimaging (60 minutes) oxytocin compared to placebo condition.
Oxytocin induced changes in stress-axis reactivity.
Cortisol concentrations assessed by blood samples after oxytocin vs. placebo administration.
Time frame: During the experimental session (approximately 4.5 hours).
Sex hormone induced changes in energy expenditure.
Changes in resting energy expenditure, measured by indirect calorimetry.
Time frame: Measured in each experimental session, approximately 4 weeks apart; between-subject outcome
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