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

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 Hauck; Bell, Richard L.; Bardo, Michael T.

doi:10.1007/s00213-018-4853-4

Cited by 12 publications

(20 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animals were trained in this phase for at least 15 days until the average EtOH consumption stabilized, i.e., there were no significant differences in average consumption across 5 consecutive sessions ( Mean = 20 days). After stable EtOH drinking was achieved, one group of animals (n=6) was pretreated with naltrexone (Experiment 1); results evaluating varenicline and r-bPiDI were reported previously (Maggio et al, 2018). A second group of animals (n=8) advanced to training for Experiment 2 (concurrent access, Phase 2) without drug pretreatment during Phase 1.…”

Section: Methodsmentioning

confidence: 96%

“…Pre-training and EtOH access (Phase 1) were conducted using procedures similar to those described by Maggio et al (2018). Briefly, during pre-training, to allow for acclimation to the taste and smell of EtOH, rats were given one bottle of 20% EtOH as the sole source of liquid for 72 consecutive hours in the home cage (Simms et al, 2010); food was available ad libitum.…”

Section: Methodsmentioning

confidence: 99%

“…During the concurrent access phase (Phase 2; Experiment 2), animals were first trained to acquire lever pressing for palatable food pellets (45 mg Dustless Precision Pellets, Bio-Serv, Frenchtown NJ) using the general methods described previously (Maggio et al, 2018) with some modifications. Rats were trained to lever press for food pellets using a standard 2-lever operant procedure (active vs inactive levers) with 2-bottle choice for EtOH (0% vs 15%) concurrently available during sessions.…”

Section: Methodsmentioning

confidence: 99%

“…A recent study from our laboratory (Maggio et al, 2018) used alcohol-preferring (P) rats, a translational genetic model of AUD (Bell et al, 2012; McBride et al, 2014), to develop a novel model of EtOH and nicotine co-use. That study used a two-bottle choice (EtOH vs water) procedure combined with a two-lever operant (active vs inactive for i.v.…”

Section: Introductionmentioning

confidence: 99%

“…It has physiochemical properties which confer greater brain penetration than bPiDI and also reduce nicotine self-administration (Beckmann et al, 2015). However, one limitation of the study by Maggio et al (2018) was that while the FR5 schedule maintained high levels of nicotine intake (>20 infusions of 0.03 mg/kg/infusion in 60 min), co-use of EtOH was relatively low (~0.5 g/kg in 60 min). Thus, the ability of varenicline and r-bPiDI to selectively decrease nicotine intake may have been due to low consumption of EtOH in the co-use phase (i.e., floor effect) or the absence/limitations of neuroadaptations associated with chronic EtOH.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Maggio

Saunders

Nixon

et al. 2018

Drug and Alcohol Dependence

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Maggio

Saunders

Nixon

et al. 2018

Drug and Alcohol Dependence

Self Cite

View full text Add to dashboard Cite

show abstract

Nicotine Self-Administration as Paradigm for Medication Discovery for Smoking Cessation: Recent Findings in Medications Targeting the Cholinergic System

Trigo

Foll

2019

Methods in Molecular Biology

View full text Add to dashboard Cite

Unequal interactions between alcohol and nicotine co-consumption: suppression and enhancement of concurrent drug intake

et al. 2019

View full text Add to dashboard Cite

Rationale Alcohol and nicotine addiction are prevalent conditions that co-occur. Despite the prevalence of co-use, factors that influence the suppression and enhancement of concurrent alcohol and nicotine intake are largely unknown.Objectives Our goals were to assess how nicotine abstinence and availability influenced concurrent alcohol consumption, and to determine the impact of quinine adulteration of alcohol on aversion resistant alcohol consumption and concurrent nicotine consumption. Methods Male and female C57BL/6J mice voluntarily consumed unsweetened alcohol, nicotine and water in a chronic 3-bottle choice procedure. In Experiment 1, nicotine access was removed for 1 week and re-introduced the following week, while the alcohol and water bottles remained available at all times. In Experiment 2, quinine (100-1000 μM) was added to the 20% alcohol bottle, while the nicotine and water bottles remained unaltered. ResultsIn Experiment 1, we found that alcohol consumption and preference were unaffected by the presence or absence of nicotine access in both male and female mice. In Experiment 2a, we found that quinine temporarily suppressed alcohol intake and enhanced concurrent nicotine, but not water, preference in both male and female mice. In Experiment 2b, chronic quinine suppression of alcohol intake increased nicotine consumption and preference in female mice without affecting water preference, whereas it increased water and nicotine preference in male mice. Conclusions Quinine suppression of alcohol consumption enhanced the preference for concurrent nicotine preference in male and female mice, suggesting that mice compensate for the quinine adulteration of alcohol by increasing their nicotine preference..

show abstract

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

Abstract: 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.

Cited by 12 publications

References 79 publications

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

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

Nicotine Self-Administration as Paradigm for Medication Discovery for Smoking Cessation: Recent Findings in Medications Targeting the Cholinergic System

Unequal interactions between alcohol and nicotine co-consumption: suppression and enhancement of concurrent drug intake

Contact Info

Product

Resources

About