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Alleviating waiting impulsivity and perseverative responding by μ-opioid receptor antagonism in two inbred mouse strains

Abstract

Rationale

Recent evidence has implicated the opioid system in exaggerated ethanol consumption and impulsivity deficits. The opioid receptor antagonist naltrexone (NTX) has proven efficient in reducing alcohol consumption; however, its role on impulsive behaviour is not fully characterised.

Objective

The aim of this study was to investigate the effects of NTX on two measures of impulsive behaviour in two inbred mouse strains that differ in ethanol preference and impulsive phenotype.

Methods

Two separate groups of C57BL/6J (B6, n = 24) and DBA2/J (D2, n = 24) male mice were exposed to intermittent ethanol (IEE; 2 g/kg) during early (PND 30–45, IEE_Early) or late (PND 45–60, IEE_Late) adolescence or the respective saline control. The ability of NTX (10 mg/kg) alone, or co-administered with ethanol (0.5 g/kg), to diminish waiting impulsivity in the five-choice serial reaction time task (5-CSRTT), or improve decision-making in a mouse version of the Iowa Gambling Task (mIGT), was examined in adulthood.

Results

In the 5-CSRTT, NTX diminished impulsivity in both strains of mice, irrespective of previous ethanol experience. In the mIGT, NTX failed to alter risky decision-making but decreased perseverative responding.

Conclusions

Blocking the actions of endogenous opioids may attenuate waiting impulsivity, in addition to alleviating perseverative responding. In a broader context, μ-opiate antagonism may be of potential interest for impulse-control disorders.

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Acknowledgments

The study was supported by the European Commission Interreg project “AlcoBinge”. The AlcoBinge project has been selected within the context of the European programme of cross-border cooperation Interreg IV A France (Channel)—England, cofinanced by ERDF.

Conflict of interest

DNS and TLR have received funding support from the GlaxoSmithKline for work on effects of opiate antagonists on ethanol consumption.

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Correspondence to David N. Stephens.

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Sanchez-Roige, S., Ripley, T.L. & Stephens, D.N. Alleviating waiting impulsivity and perseverative responding by μ-opioid receptor antagonism in two inbred mouse strains. Psychopharmacology 232, 1483–1492 (2015). https://doi.org/10.1007/s00213-014-3786-9

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Keywords

  • Alcohol
  • Naltrexone
  • C57BL/6J
  • DBA2/J
  • 5-CSRTT
  • mIGT