Browsing by Author "Saunders, Meredith A."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    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.
    (Springer, 2018-05) Maggio, Sarah E.; Saunders, Meredith A.; Baxter, Thomas A.; Nixon, Kimberly; Prendergast, Mark A.; Zheng, Guangrong; Crooks, Peter; Dwoskin, Linda P.; Slack, Rachel D.; Newman, Amy H.; Bell, Richard L.; Bardo, Michael T.; Psychiatry, School of Medicine
    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%, 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.
  • Thumbnail Image
    Item
    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
    (Elsevier, 2018-12) Maggio, Sarah E.; Saunders, Meredith A.; Nixon, Kimberly; Prendergast, Mark A.; Zheng, Guangrong; Crooks, Peter A.; Dwoskin, Linda P.; Bell, Richard L.; Bardo, Michael T.; Psychiatry, School of Medicine
    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.