An improved model of ethanol and nicotine co-use in female P rats: Effects of naltrexone, varenicline, and the selective nicotinic α6β2* antagonist r-bPiDI

Sarah E. Maggio, Meredith A. Saunders, Kimberly Nixon, Mark A. Prendergast, Guangrong Zheng, Peter A. Crooks, Linda P. Dwoskin, Richard L. Bell, Michael T. Bardo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background Although pharmacotherapies are available for alcohol (EtOH) or tobacco use disorders individually, it may be possible to develop a single pharmacotherapy to treat heavy drinking tobacco smokers by capitalizing on the commonalities in their mechanisms of action. Methods Female alcohol-preferring (P) rats were trained for EtOH drinking and nicotine self-administration in two phases: (1) EtOH alone (0 vs. 15% EtOH, 2-bottle choice) and (2) concomitant access, during which EtOH access continued with access to nicotine (0.03 mg/kg/infusion, i.v.) using a 2-lever choice procedure (active vs. inactive lever) in which the fixed ratio (FR) requirement was gradually increased to FR30. When stable co-use was obtained, rats were pretreated with varying doses of naltrexone, varenicline, or r-bPiDI, an α6β2* subtype-selective nicotinic acetylcholine receptor antagonist shown previously to reduce nicotine self-administration. Results While EtOH intake was initially suppressed in phase 2 (co-use), pharmacologically relevant intake for both substances was achieved by raising the “price” of nicotine to FR30. In phase 2, naltrexone decreased EtOH and water consumption but not nicotine intake; in contrast, naltrexone in phase 1 (EtOH only) did not significantly alter EtOH intake. Varenicline and r-bPiDI in phase 2 both decreased nicotine self-administration and inactive lever pressing, but neither altered EtOH or water consumption. Conclusions These results indicate that increasing the “price” of nicotine increases EtOH intake during co-use. Additionally, the efficacy of naltrexone, varenicline, and r-bPiDI was specific to either EtOH or nicotine, with no efficacy for co-use. Nevertheless, future studies on combining these treatments may reveal synergistic efficacy.

Original languageEnglish
Pages (from-to)154-161
Number of pages8
JournalDrug and Alcohol Dependence
Volume193
DOIs
StatePublished - Dec 1 2018

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health [grant numbers UL1 TR000117 , U19 DA17548 , P50 DA05312 , T32 DA016176 , and U24AA015512 ].

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

  • Alcohol
  • Co-use
  • Naltrexone
  • Nicotine
  • Varenicline
  • r-bPiDI

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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