Effect of Menthol on Nicotine Pharmacokinetics in Rats After Cigarette Smoke Inhalation

Abobo, Cyril V.; Ma, Ji; Liang, Dong

doi:10.1093/ntr/ntr287

Cited by 24 publications

(15 citation statements)

References 23 publications

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“…Menthol may function as a very weak inhibitor of the CYP2A6 liver enzyme, which is responsible for converting nicotine to cotinine (Kramlinger et al 2012; MacDougall et al 2003). A recent rodent study (Abobo et al 2012) excluded the possibility that menthol significantly changes the metabolism of nicotine within the same time window of the self-administration tests that were performed in the present study. The aforementioned rodent studies injected animals with menthol at doses of 100 mg/kg or higher.…”

Section: Discussionmentioning

confidence: 92%

“…However, there are no consistent reports on the possible interactions between menthol and nicotine with regard to the metabolism of these substances. Menthol was found to either slow or not change the metabolism of nicotine in humans and rodents (Abobo et al 2012; Alsharari et al 2015; Benowitz et al 2004; Benowitz et al 1999; Heck 2009). Menthol may function as a very weak inhibitor of the CYP2A6 liver enzyme, which is responsible for converting nicotine to cotinine (Kramlinger et al 2012; MacDougall et al 2003).…”

Section: Discussionmentioning

confidence: 99%

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Enhancing effect of menthol on nicotine self-administration in rats

et al. 2016

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Rationale Tobacco smoking is a leading preventable cause of premature death in the United States. Menthol is a significant flavoring additive in tobacco products. Clinical evidence suggests that menthol may promote tobacco smoking and nicotine dependence. However, it is unclear whether menthol enhances the reinforcing actions of nicotine and thus facilitates nicotine consumption. This study employed a rat model of nicotine self-administration to examine the effects of menthol on nicotine-taking behavior. Methods Male Sprague-Dawley rats were trained in daily 1-h sessions to press a lever for intravenous nicotine self-administration under a fixed-ratio 5 schedule of reinforcement. In separate groups, rats self-administered nicotine at four different doses (0.0075, 0.015, 0.03, and 0.06 mg/kg/infusion). Five minutes prior to the two test sessions, menthol (5 mg/kg) or its vehicle was administered intraperitoneally in all rats in a counterbalanced design within each group. In separate rats that self-administered 0.015 mg/kg/infusion nicotine, menthol dose-response function was determined. Menthol was also tested on food self-administration. Results An inverted U-shaped nicotine dose-response curve was observed. Menthol pretreatment shifted the nicotine dose-response curve to the left. The facilitating effect of menthol on the self-administration of 0.015 mg/kg/infusion nicotine was dose-dependent, whereas it produced similar effects at doses above the threshold of 2.5 mg/kg. Menthol tended to suppress the self-administration of food pellets. Conclusions These data demonstrate that menthol enhances the reinforcing effects of nicotine, and the effect of menthol was specific to nicotine. The findings suggest that menthol directly facilitates nicotine consumption, thereby contributing to tobacco smoking.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Enhancing effect of menthol on nicotine self-administration in rats

et al. 2016

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“…These findings are consistent with others showing no effect of non-nicotine constituents on nicotine disposition (Cao et al, 2007). However, it will be important to examine the effects of menthol-flavored EC liquids, given recent demonstrations that menthol can alter nicotine pharmacokinetics and behavioral effects (Abobo et al, 2012; Alsharari et al, 2015; Benowitz et al, 2004; Wang et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Abuse liability assessment of an e-cigarette refill liquid using intracranial self-stimulation and self-administration models in rats

LeSage

Staley

Muelken

et al. 2016

Drug and Alcohol Dependence

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Background The popularity of electronic cigarettes (ECs) has increased dramatically despite their unknown health consequences. Because the abuse liability of ECs is one of the leading concerns of the Food and Drug Administration (FDA), models to assess it are urgently needed to inform FDA regulatory decisions regarding these products. The purpose of this study was to assess the relative abuse liability of an EC liquid compared to nicotine alone in rats. Because this EC liquid contains non-nicotine constituents that may enhance its abuse liability, we hypothesized that it would have greater abuse liability than nicotine alone. Methods Nicotine alone and nicotine dose-equivalent concentrations of EC liquid were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, acquisition of self-administration, reinforcing efficacy (i.e., elasticity of demand), blockade of these behavioral effects by mecamylamine, nicotine pharmacokinetics and nicotinic acetylcholine receptor binding and activation. Results There were no significant differences between formulations on any measure, except that EC liquid produced less of an elevation in ICSS thresholds at high nicotine doses. Conclusions Collectively, these findings suggest that the relative abuse liability of this EC liquid is similar to that of nicotine alone in terms of its reinforcing and reinforcement-enhancing effects, but that it may have less aversive/anhedonic effects at high doses. The present methods may be useful for assessing the abuse liability of other ECs to inform potential FDA regulation of those products.

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“…The role of menthol cigarettes in increasing the reinforcing effects of nicotine has been recently explored in rodents (Abobo et al, 2012). Menthol has been found to alter the dopamine system in rodents by interacting with the dopamine uptake inhibitor bupropion (Umezu and Morita, 2003).…”

Section: Ways In Which Menthol Can Contribute To Addictionmentioning

confidence: 99%

Not so Cool? Menthol’s discovered actions on the nicotinic receptor and its implications for nicotine addiction

Kabbani¹

2013

Front. Pharmacol.

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Nicotine cigarette smoke is a large public health burden worldwide, contributing to various types of disease. Anti-tobacco media campaigns and control programs have significantly reduced smoking in the United States, yet trends for menthol cigarette smoking have not been as promising. Menthol cigarette smoking is particularly prevalent among young adults and African Americans, with implications for long-term impacts on health care. Continuing high rates of menthol cigarette addiction call into question the role of menthol in nicotine addiction. To date, a biological basis for the high rate of addiction and relapse among menthol cigarette smokers has not been defined. Studies have demonstrated a role for menthol in the metabolism of nicotine in the body. More recent findings now reveal an interaction between menthol and the nicotinic acetylcholine (nACh) receptor in cells. This receptor is central to the actions of nicotine in the brain, and plays an important role in nicotine addiction. The newly discovered effect of menthol on nACh receptors may begin to explain the unique addictive properties of menthol cigarettes.

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Effect of Menthol on Nicotine Pharmacokinetics in Rats After Cigarette Smoke Inhalation

Cited by 24 publications

References 23 publications

Enhancing effect of menthol on nicotine self-administration in rats

Enhancing effect of menthol on nicotine self-administration in rats

Abuse liability assessment of an e-cigarette refill liquid using intracranial self-stimulation and self-administration models in rats

Not so Cool? Menthol’s discovered actions on the nicotinic receptor and its implications for nicotine addiction

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