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

  • Robert A. Waeiss
  • Christopher P. Knight
  • Sheketha R. Hauser
  • Lauren A. Pratt
  • William J. McBride
  • Zachary A. RoddEmail author
Original Investigation


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.


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.


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.


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.


Alcohol-preferring (P) rats Alcohol Ethanol Nicotine Co-abuse Varenicline Naltrexone Maintenance Relapse Addiction 


Funding information

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

213_2019_5174_MOESM1_ESM.pdf (236 kb)
ESM 1 (PDF 236 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Psychiatry, Institute of Psychiatric ResearchIndiana University School of MedicineIndianapolisUSA

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