a differential role for neuropeptides in acute and chronic adaptive responses to alcohol behavioural and genetic analysis in caenorhabditis elegans微分作用对神经肽在急性和慢性酒精适应性反应行为和秀丽隐杆线虫的基因分析.pdfVIP

A Differential Role for Neuropeptides in Acute and Chronic Adaptive Responses to Alcohol: Behavioural and Genetic Analysis in Caenorhabditis elegans 1 1 1 2 3 Philippa Mitchell , Richard Mould , James Dillon , Steven Glautier , Ioannis Andrianakis , Christopher 3 1 1 1 James , Amanda Pugh , Lindy Holden-Dye *, Vincent O’Connor 1 School of Biological Sciences, University of Southampton, Southampton, United Kingdom, 2 School of Psychology, University of Southampton, Southampton, United Kingdom, 3 Institute of Sound and Vibration Research, University of Southampton, Southampton, United Kingdom Abstract Prolonged alcohol consumption in humans followed by abstinence precipitates a withdrawal syndrome consisting of anxiety, agitation and in severe cases, seizures. Withdrawal is relieved by a low dose of alcohol, a negative reinforcement that contributes to alcohol dependency. This phenomenon of ‘withdrawal relief’ provides evidence of an ethanol-induced adaptation which resets the balance of signalling in neural circuits. We have used this as a criterion to distinguish between direct and indirect ethanol-induced adaptive behavioural responses in C. elegans with the goal of investigating the genetic basis of ethanol-induced neural plasticity. The paradigm employs a ‘food race assay’ which tests sensorimotor performance of animals acutely and chronically treated with ethanol. We describe a multifaceted C. elegans ‘withdrawal syndrome’. One feature, decrease reversal frequency is not relieved by a low dose of ethanol and most likely results from an indirect adaptation to ethanol caused by inhibition of feeding and a food-deprived behavioural sta