A Differential Role for Neuropeptides in Acute and Chronic Adaptive Responses to Alcohol: Behavioural and Genetic Analysis in Caenorhabditis elegans

School of Biological Sciences, University of Southampton, Southampton, United Kingdom.
PLoS ONE (Impact Factor: 3.23). 05/2010; 5(5):e10422. DOI: 10.1371/journal.pone.0010422
Source: PubMed


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.

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Available from: Steven Glautier, Jan 15, 2014
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    • "C. elegans has previously been shown to display many behavioral effects of EtOH seen in other model animals. It was previously described that C. elegans displays acute intoxication, acute tolerance, EtOH preference, and withdrawal [31]–[34], [49]. Our study now adds an important fifth EtOH-induced behavior to this list: disinhibition. "
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    • "Recently, Jee et al. (2012) generated mutants for the SEB-3 receptor, an orphan corticotropin-releasing factor (CRF)-related GPCR, and showed that it is strongly implicated in the worm's stress response and ethanol tolerance. This is a perfect example of an earlier finding that several neuropeptide pathways are involved in C. elegans responses to ethanol (Mitchell et al., 2010). A genome-wide RNAi study of predicted C. elegans GPCRs was performed by Keating et al. (2003) amongst others, which were able to identify a number of neuropeptide receptors involved in reproduction and locomotion. "
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