Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice

O'Rourke, Kyu Y.; Touchette, Jillienne C.; Hartell, Elizabeth C.; Bade, Elizabeth J.; Lee, AM

doi:10.1016/j.neuropharm.2016.06.023

Cited by 20 publications

(41 citation statements)

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“…In Experiment 2b, we found that chronic suppression of alcohol consumption with increasing concentrations of quinine increased both nicotine and water preference in male mice, and only increased nicotine preference in female mice. Our previous study showed that forced alcohol abstinence produced an enhancement in concurrent nicotine consumption and preference in male and female C57BL/6J mice (O'Rourke et al, 2016). Together with this study, our work showed that alcohol intake is unresponsive to the presence or absence of the nicotine bottle, but nicotine intake is influenced by the absence of alcohol consumption or by the adulteration of the alcohol bottle with quinine.…”

Section: Discussionsupporting

confidence: 80%

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

DeBaker

Moen

Robinson

et al. 2019

Preprint

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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.3

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Section: Discussionsupporting

confidence: 80%

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

DeBaker

Moen

Robinson

et al. 2019

Preprint

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“…Additionally, the effect of sazetidine-A has never been tested in mice, nor on voluntary, oral co-consumption of alcohol and nicotine presented concurrently. In this study, we tested the effect of sazetidine-A on alcohol and nicotine consumption in male and female mice using models of voluntary, oral consumption that we developed and have described previously (O’Rourke et al, 2016). Here, we show for the first time that sazetidine-A, at a dose that does not affect water or saccharin consumption, reduces alcohol consumption in mice without affecting nicotine consumption.…”

Section: Introductionmentioning

confidence: 99%

The nicotinic receptor drug sazetidine-A reduces alcohol consumption in mice without affecting concurrent nicotine consumption

et al. 2018

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Alcohol and nicotine addiction are frequently co-morbid. The nicotinic acetylcholine receptors (nAChRs) are critical for both alcohol and nicotine addiction mechanisms, since nAChR drugs that reduce nicotine consumption have been shown to also reduce alcohol consumption. Sazetidine-A, a pre-clinical nAChR drug with agonist and desensitizing effects at α4β2 and α7 nAChRs, has been reported to reduce alcohol consumption and nicotine self-administration in rats when administered at high doses. However, this effect has not been replicated in mice. In this study, we examined the effect of sazetidine-A on alcohol and nicotine consumption in male and female mice utilizing voluntary oral consumption procedures previously developed in our lab. We found that sazetidine-A (1 mg/kg, i.p) reduced overnight alcohol consumption, but did not affect nicotine consumption when presented either alone or concurrently with alcohol. Sazetidine-A did not reduce water or saccharin consumption at any dose tested. In a chronic co-consumption experiment in which either alcohol or nicotine was re-introduced after one week of forced abstinence, sazetidine-A attenuated post-abstinence consumption of alcohol but not nicotine. Sazetidine-A also significantly reduced alcohol consumption in an acute, binge drinking-in-the-dark procedure. Finally, we tested the effect of sazetidine-A on alcohol withdrawal, and found that sazetidine-A significantly reduced handling-induced convulsions during alcohol withdrawal. Collectively, these data suggest a novel role for the nAChR targets of sazetidine-A in specifically mediating alcohol consumption, separate from the involvement of nAChRs in mediating nicotine consumption. Delineation of this pathway may provide insight into novel therapies for the treatment of alcohol use disorders.

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“…4 Similar sex differences have been observed in rodent models. Female C57BL/6 mice consume more alcohol and nicotine in a two-bottle choice procedure, 22 are less sensitive to nicotine-induced locomotor activity, and show more anxiogenic behavior in response to nicotine compared to male animals. 45 Sex hormones can modulate the reward system, and estradiol itself can influence gene transcription in neurons.…”

Section: Sex Differences In Nachr-dependent Behaviorsmentioning

confidence: 96%

Bidirectional sex-dependent regulation of α6 and β3 nicotinic acetylcholine receptors by protein kinase Cε

Moen

DeBaker

Myjack

et al. 2020

Preprint

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Nicotine and alcohol are the most commonly abused substances worldwide, and comorbid nicotine and alcohol addiction is highly prevalent. Nicotinic acetylcholine receptors (nAChRs) containing the α6 and β3 subunits are expressed in neural reward circuits and are critical for both nicotine and alcohol reward. nAChRs are dynamically regulated by signaling molecules such as protein kinase C epsilon (PKCε), which impact transcription of α6 and β3 subunit mRNA (Chrna6 and Chrnb3, respectively). Previous work found decreased expression of Chrna6 and Chrnb3 transcripts in the ventral midbrain of male PKCε -/mice, who also consume less nicotine and alcohol compared to wild-type (WT) littermates. Here, we show that female PKCε -/mice have enhanced expression of Chrna6 and Chrnb3 transcripts in the ventral midbrain, which functionally impacts nAChR-dependent behavior, as female but not male PKCε -/mice exhibit locomotor hypersensitivity to nicotine. Female PKCε -/mice show no differences in alcohol-induced sedation compared to WT littermates, while male PKCε -/have enhanced sedation compared to WT mice, a phenotype that has previously been reported in α6 -/mice.Female PKCε -/mice also show reduced depression-like behavior in response to systemic injections of varenicline compared to WT littermates, and this effect was absent in male mice.Additionally, we found that female PKCε -/mice show altered alcohol and nicotine consumption patterns in chronic voluntary two bottle choice assays. Our data reveal a bidirectional effect of sex in the transcriptional regulation of nicotinic receptors by PKCε, and highlight the importance of studying both sexes in preclinical animal models.

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Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice

Cited by 20 publications

References 50 publications

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

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

The nicotinic receptor drug sazetidine-A reduces alcohol consumption in mice without affecting concurrent nicotine consumption

Bidirectional sex-dependent regulation of α6 and β3 nicotinic acetylcholine receptors by protein kinase Cε

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