Neuroadaptation in Nicotine Addiction: Update on the Sensitization-Homeostasis Model

Abstract: The role of neuronal plasticity in supporting the addictive state has generated much research and some conceptual theories. One such theory, the sensitization-homeostasis (SH) model, postulates that nicotine suppresses craving circuits, and this triggers the development of homeostatic adaptations that autonomously support craving. Based on clinical studies, the SH model predicts the existence of three distinct forms of neuroplasticity that are responsible for withdrawal, tolerance and the resolution of withdrawal. Over the past decade, many controversial aspects of the SH model have become well established by the literature, while some details have been disproven. Here we update the model based on new studies showing that nicotine dependence develops through a set sequence of symptoms in all smokers, and that the latency to withdrawal, the time it takes for withdrawal symptoms to appear during abstinence, is initially very long but shortens by several orders of magnitude over time. We conclude by outlining directions for future research based on the updated model, and commenting on how new experimental studies can gain from the framework put forth in the SH model.