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 language | English |
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Pages (from-to) | 154-161 |
Number of pages | 8 |
Journal | Drug and Alcohol Dependence |
Volume | 193 |
DOIs | |
State | Published - Dec 1 2018 |
Bibliographical note
Publisher Copyright:© 2018 Elsevier B.V.
Funding
This work was supported by the National Institutes of Health [grant numbers UL1 TR000117 , U19 DA17548 , P50 DA05312 , T32 DA016176 , and U24AA015512 ].
Funders | Funder number |
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National Institutes of Health (NIH) | UL1 TR000117, U24AA015512, T32 DA016176, U19 DA17548 |
National Institutes of Health (NIH) | |
National Institute on Drug Abuse | P50DA005312 |
National Institute on Drug Abuse |
Keywords
- Alcohol
- Co-use
- Naltrexone
- Nicotine
- Varenicline
- r-bPiDI
ASJC Scopus subject areas
- Toxicology
- Pharmacology
- Psychiatry and Mental health
- Pharmacology (medical)