Insight of molecular and neural mechanisms of general anesthesia from invertebrate animal model Drosophila melanogaster

General anesthesia (GA) is a drug induced reversible state of unconsciousness, amnesia, analgesia, and immobility in response to pain. Accumulating studies using animal models have shown several mechanisms of the action and optimization of GA, including disruption of brain functional connectivity, regulation of multiple neural pathways, and modulation of specific receptors or ion channels. Despite recent efforts to study mechanisms of neurotransmission and cell signaling, further investigation is still required to facilitate the development of safer and more effective strategies to minimize risks and to unlock new functions of anesthesia within the brain. Here, we focus on findings from Drosophila melanogaster, a dedicated animal model that has provided pioneering insights into mammalian studies, which benefit from its powerful genetic tools, advanced imaging techniques, and economic neural network. In this review, we summarize and review: 1) paradigms for the evaluation of response to GA in Drosophila; 2) molecular targets and their functional mechanisms; and 3) characterized neuronal activities and identified neural circuits shared by GA and sleep. We also attempt to provide some thinking based on conservative mechanisms from a cross-species perspective.