Maggio, Sarah E.Saunders, Meredith A.Baxter, Thomas A.Nixon, KimberlyPrendergast, Mark A.Zheng, GuangrongCrooks, PeterDwoskin, Linda P.Slack, Rachel D.Newman, Amy H.Bell, Richard L.Bardo, Michael T.2019-07-252019-07-252018-05Maggio, S. E., Saunders, M. A., Baxter, T. A., Nixon, K., Prendergast, M. A., Zheng, G., … Bardo, M. T. (2018). 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. Psychopharmacology, 235(5), 1439–1453. https://doi.org/10.1007/s00213-018-4853-40033-3158https://hdl.handle.net/1805/19962Rationale: 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%, 2-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.en-USPublisher Policy(R)-modafinilAlcoholCo-useEthanolNicotineR-bPiDIVareniclineArticle