influence of dopaminergic blockade on stress responses, motivation and emotional reactivity in humans.

Conditions: Healthy Participants

Summary: the study aims to identify whether partial blockade of human dopamine signaling with antipsychotic drugs affects human stress responses, motivation and emotion. 84 healthy adult participants are planned to complete the study protocol. therefore three experiments are planned: experiment 1: influence of amisulpride on human stress responses. experiment 2: influence of amisulpride on motivated effort. experiment 3: influence of amisulpride on emotion.

the study is a double blind, placebo controlled, randomized trial with two groups. one group will be receiving placebo (pg) and the other group will receive 300 mg amisulpride (vg). all participants are planned to complete all three experiments sequentially after drug/placebo intake. in experiment 1 we want to test whether a medium single dosage of amisulpride (vg) changes human stress responses compared to the pg. therefore test subjects take the medication / placebo and wait for peak plasma levels. afterwards they undergo a standardized stress test (mast procedure,e.g. shilton et al., 2017) where they submerge their non-dominant hand in cold water and have to do mental arithmetic tasks. we collect ecg, cortisol and skin conductance data as well as subjective measures of the stress response. in experiment 2 that is done after completion of experiment 1 the aim is testing whether the vg compared to the pg has an altered motivated effort. therefore so called effort based paradigms (reddy et al., 2015) are used. in these paradigms participants are given the option between an easy and effortless way of solving a trial that is reinforced with a small monetary reward or a harder and effortful way of trial solving that is rewarded higher. we measure how often the vg versus the pg will take the easy, low reward option over the hard, high reward option. in experiment 3 and after the completion of experiment to the aim is it to test whether the mean intensity of visually evoked emotions in the vg is changed compared to the pg. therefore we use a stimulus set (15 positive images, 15 negative images, 15 neutral images) out of the international affective picture system images to evoke emotions and plan to analyze data like in positivity offset research (detailed description in: strauss et al, 2017).

Eligibility criteria:
inclusion criteria: * common european framework of reference for languages level b2 in german language. * consent ability for all relevant aspects of the experiment. exclusion criteria: * amisulpride allergy. * allergy to other components of amisulpride / placebo capsules like lactose. * daily intake of other medication including contraceptives. * tendency to seizures. * diagnosis of cancer especially pheochromocytoma, prolactinoma, or breast cancer. * kidney dysfunction: creatinine clearance below 10 ml per minute. * high risk for stroke or thrombosis. * known prolongation of the qt interval, * any substantial medical condition that is capable of reducing the volunteers ability to participate at the study. * suicidal thoughts or suicide attempts in the past or at present. * substantial mental disorders especially schizophrenia, bipolar disorder, drug abuse, or personality disorders. * pregnancy or breastfeeding.

Keywords: dopamine antagonists dopamine blockade psychophysiological stress response maastricht acute stress test (mast) effort based paradigms positivity offset theory international affective picture system (iaps)