A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in caenorhabditis elegans


Mitchell, Philippa, Mould, Richard, Dillon, James, Glautier, Steven, Andrianakis, Ioannis, James, Christopher, Pugh, Amanda, Holden-Dye, Lindy and O'Connor, Vincent, Hart, Anne C. (ed.) (2010) A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in caenorhabditis elegans. PLoS ONE, 5, (5), e10422. (doi:10.1371/journal.pone.0010422).

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Description/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 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.

Item Type: Article
ISSNs: 1932-6203 (electronic)
Related URLs:
Subjects: R Medicine > R Medicine (General)
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 152569
Date Deposited: 26 May 2010 13:32
Last Modified: 27 Mar 2014 19:11
URI: http://eprints.soton.ac.uk/id/eprint/152569

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