Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and DAT inhibitor (R)-modafinil on co-use of ethanol and nicotine in female P rats

Authors

Sarah E. Maggio, University of KentuckyFollow
Meredith A. Saunders, University of KentuckyFollow
Thomas A. Baxter, University of Kentucky
Kimberly Nixon, University of KentuckyFollow
Mark A. Prendergast, University of KentuckyFollow
Guangrong Zheng, University of Arkansas at Little Rock
Peter A. Crooks, University of Arkansas for Medical SciencesFollow
Linda P. Dwoskin, University of KentuckyFollow
Rachel D. Slack, National Institute on Drug Abuse
Amy H. Newman, National Institute on Drug Abuse
Richard L. Bell, Indiana University School of Medicine

Abstract

Rationale: Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use.

Objectives: Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs. 15%, two-bottle choice), (2) nicotine alone (0.03 mg/kg/infusion, active vs. inactive lever), and (3) concurrent access to both EtOH and nicotine. Using this model, we examined the effects of (1) varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist with high affinity for the α4β2* subtype; (2) r-bPiDI, a subtype-selective antagonist at α6β2* nAChRs; and (3) (R)-modafinil, an atypical inhibitor of the dopamine transporter (DAT).

Results: In phases 1 and 2, pharmacologically relevant intake of EtOH and nicotine was achieved. In the concurrent access phase (phase 3), EtOH consumption decreased while nicotine intake increased relative to phases 1 and 2. For drug pretreatments, in the EtOH access phase (phase 1), (R)-modafinil (100 mg/kg) decreased EtOH consumption, with no effect on water consumption. In the concurrent access phase, varenicline (3 mg/kg), r-bPiDI (20 mg/kg), and (R)-modafinil (100 mg/kg) decreased nicotine self-administration but did not alter EtOH consumption, water consumption, or inactive lever pressing.

Conclusions: These results indicate that therapeutics which may be useful for smoking cessation via selective inhibition of α4β2* or α6β2* nAChRs, or DAT inhibition, may not be sufficient to treat EtOH and nicotine co-use.

Document Type

Article

Publication Date

2018

Notes/Citation Information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Digital Object Identifier (DOI)

https://doi.org/10.1007/s00213-018-4853-4

Funding Information

Supported by NIH grants R01AA025591, UL1TR000117, U19DA17548, P50DA05312, T32DA016176, and U24AA015512.

Repository Citation

Maggio, Sarah E.; Saunders, Meredith A.; Baxter, Thomas A.; Nixon, Kimberly; Prendergast, Mark A.; Zheng, Guangrong; Crooks, Peter A.; Dwoskin, Linda P.; Slack, Rachel D.; Newman, Amy H.; and Bell, Richard L., "Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and DAT inhibitor (R)-modafinil on co-use of ethanol and nicotine in female P rats" (2018). Psychology Faculty Publications. 263.
https://uknowledge.uky.edu/psychology_facpub/263