Insight into molecular and neural mechanisms of general anesthesia from the invertebrate model Drosophila melanogaster.

General anesthesia (GA) is a pharmacologically induced, reversible state characterized by unconsciousness, amnesia, analgesia, and immobility in response to noxious stimuli. Accumulating evidence from animal models has elucidated diverse mechanisms of the action underlying GA, including disruption of large-scale brain network connectivity, regulation of multiple neural pathways, and modulation of specific receptors and ion channels. Despite advances in dissecting the neurobiological basis of anesthetic action, the precise cellular and circuit-level processes remain incompletely understood, limiting the development of safer and more effective strategies. Recent studies in Drosophila melanogaster, a genetically tractable model organism offering robust genetic analysis, advanced imaging capabilities, and compact neural architecture, have yielded critical insights into the conserved neurobiological mechanisms of GA, offering translational value for mammalian systems. This review outlines: 1) experimental paradigms used to evaluate anesthetic sensitivity and behavioral responses in Drosophila; 2) molecular targets and their mechanistic roles in mediating GA; and 3) neural circuit architectures and activity patterns shared by GA and sleep. Cross-species comparisons are integrated to highlight conserved mechanisms that may guide the development of more refined anesthetic strategies.