Adult mice voluntarily progress to nicotine dependence in an oral self-selection assay

Locklear, Laura L.; McDonald, Craig G.; Smith, Robert F.; Fryxell, Karl J.

doi:10.1016/j.neuropharm.2012.04.037

Cited by 23 publications

(30 citation statements)

References 76 publications

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“…However, with extended access it is likely that upregulation would be seen given the high levels of intake in the current studies. Similar intakes have also been shown to result in somatic withdrawal symptoms during 28 days of access, but not 14, indicating that the duration of access in the current studies may not produce somatic withdrawal (Grabus et al, 2004 Locklear et al, 2012). Questions of cotinine levels, somatic withdrawal, and nAChR upregulation can be answered with time-course studies.…”

Section: Discussionsupporting

confidence: 53%

“…The current binge-like model presents a simple and quick pre-clinical paradigm to assess potential treatments for smoking cessation, as well as smoking and ethanol disorders. Avenues for future research include reducing nicotine and saccharin concentrations, analyzing the time course of nicotine intake during concurrent ethanol access, and assessing the parameters of the models in females, which have previously been shown to have higher levels of 24-hour free-choice intake (Glatt et al, 2009; Klein et al, 2004; Locklear et al, 2012; Meliska et al, 1995). Most importantly, a time-course of cotinine levels should be assessed during and after nicotine exposure.…”

Section: Discussionmentioning

confidence: 99%

“…C57Bl/6J (B6) mice have routinely been shown to consume more nicotine than other strains in 24 hr free- choice access paradigms. Relatively high levels of intake are consistent across nicotine concentration (Glatt et al, 2009; Klein et al, 2004; Locklear et al, 2012) and are not changed when a sweetener is introduced to the nicotine and non-nicotine solution or related to intake of sweetened solutions (Meliska et al, 1995; Robinson et al, 1996). These results may suggest that B6 mice are insensitive to the bitter taste of quinine relative to other inbred strains, particularly at higher concentrations.…”

Section: Introduction1mentioning

confidence: 99%

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Developing a model of limited-access nicotine consumption in C57Bl/6J mice

Kasten

Frazee

Boehm

2016

Pharmacology Biochemistry and Behavior

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Although United States smoking rates have been on the decline over the past few decades, cigarette smoking still poses a critical health and economic threat. Very few treatment options for smoking exist, and many of them do not lead to long-term abstinence. Preclinical models are necessary for understanding the effects of nicotine and developing treatments. Current self-administration models of nicotine intake may require surgical procedures and often result in low levels of intake. Further, they do not lend themselves to investigating treatments. The current study sought to develop a limited-access model of nicotine intake using the Drinking-in-the-Dark paradigm, which results in high levels of binge-like ethanol consumption that can be pharmacologically manipulated. The present study found that mice will consume nicotine under a range of parameters. Intakes under the preferred condition of 0.14 mg/ml nicotine in 0.2% saccharin reached over 6 mg/kg in two hours and were reduced by an injection of R(+)-baclofen. Mecamylamine did not significantly affect nicotine consumption. As nicotine and ethanol are often co-abused, nicotine intake was also tested in the presence of ethanol. When presented in the same bottle, mice altered nicotine intake under various concentrations to maintain consistent levels of ethanol intake. When nicotine and ethanol were presented in separate bottles, mice greatly reduced their nicotine intake while maintaining ethanol intake. In conclusion, these studies characterize a novel model of limited-access nicotine intake that can be pharmacologically manipulated.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Introduction1mentioning

confidence: 99%

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Developing a model of limited-access nicotine consumption in C57Bl/6J mice

Kasten

Frazee

Boehm

2016

Pharmacology Biochemistry and Behavior

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“…For example, in mice with very rapid rates of nicotine metabolism, small differences in levels or function of CYP2A5 between different mouse strains may result in substantially differing nicotine pharmacological effects. Thus, pharmacokinetic differences likely contribute to differences in effects seen between studies employing the use of different mouse strains (Locklear, McDonald, Smith, & Fryxell, 2012;Wilking et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamics Studies of Nicotine After Oral Administration in Mice: Effects of Methoxsalen, a CYP2A5/6 Inhibitor

AlSharari

Siu

Tyndale

et al. 2013

Nicotine & Tobacco Research

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“…Very few groups have performed studies of voluntary oral alcohol and intravenous nicotine self-administration in male rats (Lê et al, 2010; Lê et al, 2014; Scuppa et al, 2015). Due to the technical challenges of intravenous self-administration in mice, nicotine consumption is most often studied using voluntary oral consumption procedures (Klein et al, 2004; Lee and Messing, 2011; Locklear et al, 2012). Alcohol consumption has long been studied using a variety of oral consumption procedures in mice (Rhodes et al, 2005; Hwa et al, 2011; Lee et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction.

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Adult mice voluntarily progress to nicotine dependence in an oral self-selection assay

Cited by 23 publications

References 76 publications

Developing a model of limited-access nicotine consumption in C57Bl/6J mice

Developing a model of limited-access nicotine consumption in C57Bl/6J mice

Pharmacokinetic and Pharmacodynamics Studies of Nicotine After Oral Administration in Mice: Effects of Methoxsalen, a CYP2A5/6 Inhibitor

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

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