How Does the Opioid System Shape Stress and Social Behaviour in Men and Women and What Role Does Childhood Unpredictability Play?

While opioid use disorder presents a rising public health concern, the underlyingneurobiological mechanisms of substance use are not well understood. In animal studies,activation of the Mu Opioid Receptor (MOR) system has been shown to have stress‐bufferingeffects and to decrease affiliative behaviour, which is in line with addiction modelspostulating impaired stress response and poor social interactions to be risk indicatorsfor addiction pathogenesis. In humans however, this has not been consistently found.Importantly, behavioural pharmacology studies have often been restricted to male testsubjects or have been underpowered. Therefore, a significant knowledge gap remainsregarding sex‐specific differences in MOR activation. The additional impact of chronicstress in the form of early life stress significantly affects brain development, in turnshaping stress reactivity and affiliative behaviour in later life. This forms the basisof the research question of the present study, whether sex and childhood unpredictabilitymodulate the effects of MOR activation on stress response and social interactionbehaviour.The prototypical opioid morphine will be used to activate the MOR. Participants willreceive the study medication on two separate visits in a randomised, counterbalancedorder. Afterwards, participants will conduct computer‐based stress and social interactiontasks.Learning more about individual differences in MOR activation and its effects on stressand social behaviour can help to uncover vulnerability and risk factors for opioid usedisorder and improve personalised treatment opportunities.