Moxie begets MOXI: The journey to a novel hypothesis about Mu-opioid and OXytocin system Interactions

This narrative review summarizes the early life of the author, Khalin E. Nisbett, and highlights the factors that led to her career in research and her development of two novel research hypotheses: the Mu-opioid and OXytocin system Interaction (MOXI) hypothesis and Mu-Opioid receptor antagonist and OXytocin receptor Agonist In Combination (MOXAIC) treatment hypothesis. Notably, Nisbett's career began in the era after countless studies demonstrated that oxytocin is not just a female neurotransmitter and not just a female reproductive hormone, an era in which researchers are exploring the role of oxytocin in emotion regulation, social interaction, and cognitive processing across both sexes. As such, the previously held perspective that oxytocin is “just a female hormone” did not impede Nisbett's ideas. Intrigued by science, emotion regulation, and social interaction, she began to explore the role of oxytocin and opioids in emotion regulation. On the heels of earlier theories, such as the Tend-and-Befriend theory and Opioid Theory of Social Attachment, she began to develop the MOXI hypothesis, which postulates that the μ-opioid receptor and oxytocin systems interact to mediate social interaction and emotion regulation. In this narrative review, Nisbett summarizes two studies that explored (i) the role of oxytocin in anxiety- and depression-like behavior and (ii) the effect of opioid receptor blockade on the anxiolytic-like effect of oxytocin, which led to a revision of the MOXI hypothesis and postulation of the Mu−Opioid receptor antagonist and OXytocin receptor Agonist In Combination (MOXAIC) treatment hypothesis. Nisbett also discusses several limitations of these hypotheses and her current research interests and aspirations.