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Ethanol is a widely used beverage and abused drug. Alcoholism causes severe damage to human health and creates serious social problems. Understanding the mechanisms underlying ethanol actions is important for the development of effective therapies. Alcohol has a wide spectrum of effects on physiological activities and behaviours, from sensitization to sedation and even intoxication with increasing concentrations. Animals develop tolerance to ethanol. However, the underlying mechanisms are not well understood. In  Caenorhabditis elegans , NPR-1 negatively regulates the development of acute tolerance to ethanol. Here, using  in vivo  Ca 2+  imaging, behavioural tests and chemogenetic manipulation, we show that the soluble guanylate cyclase complex GCY-35/GCY-36—TAX-2/TAX-4 signalling pathway in O 2  sensory neurons positively regulates acute functional tolerance in  npr-1  worms.

GCY-35/GCY-36—TAX-2/TAX-4 Signalling in O2 Sensory Neurons Mediates Acute Functional Ethanol Tolerance in Caenorhabditis elegans