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Calcium chloride mimics the effects of acamprosate on cognitive deficits in chronic alcohol-exposed mice

Abstract

Rationale

Acamprosate (calcium-bis N-acetylhomotaurinate) is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Acamprosate can improve executive functions that are impaired by chronic intermittent ethanol (CIE) exposure. Recent work has suggested that acamprosate’s effects on relapse prevention are due to its calcium component, which raises the question whether its pro-cognitive effects are similarly mediated by calcium.

Objectives

This study examined the effects of acamprosate on alcohol-induced behavioral deficits and compared them with the effects of the sodium salt version of N-acetylhomotaurinate or calcium chloride, respectively.

Methods

We exposed mice to alcohol via three cycles of CIE and measured changes in alcohol consumption in a limited-access paradigm. We then compared the effects of acamprosate and calcium chloride (applied subchronically for 3 days during withdrawal) in a battery of cognitive tasks that have been shown to be affected by chronic alcohol exposure.

Results

CIE-treated animals showed deficits in attentional set-shifting and deficits in novel object recognition. Alcohol-treated animals showed no impairments in social novelty detection and interaction, or delayed spontaneous alternation. Both acamprosate and calcium chloride ameliorated alcohol-induced cognitive deficits to comparable extents. In contrast, the sodium salt version of N-acetylhomotaurinate did not reverse the cognitive deficits.

Conclusions

These results add evidence to the notion that acamprosate produces its anti-relapse effects through its calcium moiety. Our results also suggest that improved regulation of drug intake by acamprosate after withdrawal might at least in part be related to improved cognitive function.

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NIAAA 1RO3AA023268 (SK).

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Correspondence to Sven Kroener.

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The study was approved by the Institutional Animal Care and Use Committee of the University of Texas at Dallas.

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Pradhan, G., Melugin, P.R., Wu, F. et al. Calcium chloride mimics the effects of acamprosate on cognitive deficits in chronic alcohol-exposed mice. Psychopharmacology 235, 2027–2040 (2018). https://doi.org/10.1007/s00213-018-4900-1

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  • DOI: https://doi.org/10.1007/s00213-018-4900-1

Keywords

  • Acamprosate
  • Calcium
  • Attentional set-shifting
  • Novel object recognition
  • Alcohol addiction