TY - JOUR T1 - A Differential Role for Neuropeptides in Acute and Chronic Adaptive Responses to Alcohol: Behavioural and Genetic Analysis in Caenorhabditis elegans A1 - Mitchell, Philippa A1 - Mould, Richard A1 - Dillon, James A1 - Glautier, Steven A1 - Andrianakis, Ioannis A1 - James, Christopher A1 - Pugh, Amanda A1 - Holden-Dye, Lindy A1 - O'Connor, Vincent Y1 - 2010/05/03 N2 - 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 state. However another aspect, an aberrant behaviour consisting of spontaneous deep body bends, did show withdrawal relief and therefore we suggest this is the expression of ethanol-induced plasticity. The potassium channel, slo-1, which is a candidate ethanol effector in C. elegans, is not required for the responses described here. However a mutant deficient in neuropeptides, egl-3, is resistant to withdrawal (although it still exhibits acute responses to ethanol). This dependence on neuropeptides does not involve the NPY-like receptor npr-1, previously implicated in C. elegans ethanol withdrawal. Therefore other neuropeptide pathways mediate this effect. These data resonate with mammalian studies which report involvement of a number of neuropeptides in chronic responses to alcohol including corticotrophin-releasing-factor (CRF), opioids, tachykinins as well as NPY. This suggests an evolutionarily conserved role for neuropeptides in ethanol-induced plasticity and opens the way for a genetic analysis of the effects of alcohol on a simple model system. JF - PLOS ONE JA - PLOS ONE VL - 5 IS - 5 UR - https://doi.org/10.1371/journal.pone.0010422 SP - e10422 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pone.0010422 ER -