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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. doi:10.1371/journal.pone.0010422
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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 | ||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
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| Divisions: | Faculty of Science > 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: |
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| 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 | ||||
| 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) |
Data sourced from Thomson Reuters' Web of Knowledge
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