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A differential role for neuropeptide signalling in acute and chronic adaptive responses to alcohol: Behavioural and genetic analysis in Caenorhabditis elegans

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Hart, Anne C., Mitchell, Philippa, Mould, Richard, Dillon, James, Glautier, Steve, Andrianakis, Ioannis, James, C. J., Pugh, Amanda, Holden-Dye, Lindy and O'Connor, Vincent. (2010) A differential role for neuropeptide signalling in acute and chronic adaptive responses to alcohol: Behavioural and genetic analysis in Caenorhabditis elegans. PLoS One, Vol.5 (No.5). Article: e10422. ISSN 1932-6203

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Official URL: http://dx.doi.org/10.1371/journal.pone.0010422

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:

Journal Article

Subjects:

Q Science > QP Physiology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

Divisions:

Faculty of Science > WMG (Formerly the Warwick Manufacturing Group)

Journal or Publication Title:

PLoS One

Publisher:

Public Library of Science

ISSN:

1932-6203