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Therapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats

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Abstract

Rationale and objectives

Simultaneous alcohol and nicotine consumption occurs in the majority of individuals with alcohol use disorder (AUD) and nicotine dependence. Varenicline (Var) is used to assist in the cessation of nicotine use, while naltrexone (Nal) is the standard treatment for AUD. Despite evidence that ethanol (EtOH) and nicotine (NIC) co-use produces unique neuroadaptations, preclinical research has focused on the effects of pharmacotherapeutics on a single reinforcer. The current experiments examined the effects of Var and Nal on EtOH, NIC, or EtOH+NIC intake.

Methods

Animals were randomly assigned to one of four drinking conditions of 24-h access to a three-bottle choice paradigm, one of which always contained water. Drinking conditions were water only, 0.07 and 0.14 mg/mL NIC (NIC only), 15% and 30% EtOH (EtOH only), or 15% and 30% EtOH with 0.14 mg/mL NIC (EtOH+NIC). The effects of Var (0, 1, or 2 mg/kg) or Nal (0, 1, or 10 mg/kg) injections on maintenance and relapse consumption were determined during four consecutive days.

Results

Var reduced maintenance and relapse NIC intake but had no effect on EtOH or EtOH+NIC drinking. Conversely, Nal reduced EtOH maintenance and relapse drinking, but had no effect on NIC or EtOH+NIC drinking.

Discussion

The results indicate the standard pharmacological treatments for nicotine dependence and AUD were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC co-use/abuse. These findings suggest that co-abuse may promote unique neuroadaptations that require models of polysubstance abuse to develop pharmacotherapeutics to treat AUD and nicotine dependence.

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Funding

This study was supported by NIAAA grants AA07611, AA07462, AA10721, AA20908, and AA019366.

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Authors and Affiliations

  1. Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Robert A. Waeiss & Lauren A. Pratt

  2. Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 W. 15th Street, Suite 300B, Indianapolis, IN, 46202-2266, USA

    Christopher P. Knight, Sheketha R. Hauser, William J. McBride & Zachary A. Rodd

Authors
  1. Robert A. Waeiss
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  2. Christopher P. Knight
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  3. Sheketha R. Hauser
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  4. Lauren A. Pratt
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  5. William J. McBride
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  6. Zachary A. Rodd
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Correspondence to Zachary A. Rodd.

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Waeiss, R.A., Knight, C.P., Hauser, S.R. et al. Therapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats. Psychopharmacology 236, 1887–1900 (2019). https://doi.org/10.1007/s00213-019-5174-y

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