Given the complex etiology of alcohol abuse disorders and dependence, characterized by brain-wide pathophysiological alterations under continuous crosstalk, we reason that to better understand and treat alcohol abuse, we need to develop organ and system-wide models (even if initially incomplete and speculative to some extent) with the potential to capture the dynamism in such complexity. Once we discover main dynamic relationships conducive to stable states of the disease, we may be able to design strategies to detour or reverse disease progression, akin of chemical reactions transiting through multiple equilibrium states. From the analysis and hypothetical models presented here, the notion emerges that miRNAs are efficiently being upregulated in response to alcohol insult and consequently inducing organ and system-wide homeostatic changes that produce long-term adaptation under the specific cellular environment. Remarkably, miRNAs that localize to and display activity at synapses in neurons are also capable of eliciting distinct and specific activities in other cell types, such as innate immunity-related functions in microglial cells, among others. This underscores the impact that molecular efficiency, signaling crosstalk, and cellular economy plays in the adaptation
