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. doi:10.1371/journal.pone.0010422 ISSN 1932-6203.

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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, Engineering and Medicine > Engineering > WMG (Formerly the Warwick Manufacturing Group)
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	3 May 2010
Dates:	Date Event 3 May 2010 Published
Volume:	Vol.5
Number:	No.5
Number of Pages:	17
Page Range:	Article: e10422
DOI:	10.1371/journal.pone.0010422
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Medical Research Council (Great Britain) (MRC), British Pharmacological Society (BPS), National Institutes of Health/National Center for Research Resources (NIH-NCRR)

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