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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.
Document Type
Article
Publication Date
2018
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.drugalcdep.2018.09.008
Funding Information
This work was supported by the National Institutes of Health [grant numbers UL1 TR000117, U19 DA17548, P50 DA05312, T32 DA016176, and U24AA015512].
Repository Citation
Maggio, Sarah E.; Saunders, Meredith A.; Nixon, Kimberly; Prendergast, Mark A.; Zheng, Guangrong; Crooks, Peter A.; Dwoskin, Linda P.; Bell, Richard L.; and Bardo, Michael T., "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" (2018). Psychology Faculty Publications. 238.
https://uknowledge.uky.edu/psychology_facpub/238
Notes/Citation Information
0376-8716/ © 2018 Elsevier B.V. All rights reserved.