The Role of Menthol in Cigarettes as a Reinforcer of Smoking Behavior

Ahijevych, Karen; Garrett, Bridgette E.

doi:10.1093/ntr/ntq203

Cited by 110 publications

(90 citation statements)

References 34 publications

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“…We observed this menthol-dependent decrease or abolition of nicotine reward-related behavior, despite recent data that simultaneous exposure to menthol and nicotine enhances nicotine reward and reinforcement (Gandhi et al, 2009;Ahijevych and Garrett, 2010;Wang et al, 2014). These contrasting observations point to the fact that menthol may act differently alone than when combined with nicotine.…”

Section: Chronic Menthol Abolishes Nicotine Reward-like Behaviorcontrasting

confidence: 85%

“…Previous data show that menthol acts in the lungs (Ahijevych and Garrett, 2010) with mice and with cultured DA neurons in the absence of nicotine, we conclude that menthol exerts a neural effect(s) by itself, in addition to modifications that may occur when nicotine is present. In using osmotic minipumps to deliver menthol to mice, we largely avoid the pharmacokinetics of exposure through the lungs.…”

Section: Menthol May Act Directly On Midbrain Da Neuronssupporting

confidence: 63%

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Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward

et al. 2016

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Upregulation of ␤2 subunit-containing (␤2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate ␤2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of ␣4 and ␣6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of ␣4* nAChRs, complementing that of chronic nicotine alone, which upregulates ␣4 subunit-containing (␣4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nM menthol alone also increased nAChR number and favored the formation of (␣4) 3 (␤2) 2 nAChRs; this contrasts with the action of nicotine itself, which favors (␣4) 2 (␤2) 3 nAChRs. Menthol alone also increases the number of ␣6␤2 receptors that exclude the ␤3 subunit. Thus, menthol stabilizes lower-sensitivity ␣4* and ␣6 subunitcontaining nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway.

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Section: Chronic Menthol Abolishes Nicotine Reward-like Behaviorcontrasting

confidence: 85%

Section: Menthol May Act Directly On Midbrain Da Neuronssupporting

confidence: 63%

Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward

et al. 2016

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“…For example, adding menthol flavorings to cigarettes produces a smoke that is perceived to be less harsh than nonmenthol cigarette smoke (Hymowitz et al, 1995). Focus group interviews suggest that "taste" is the most common reason for smoking menthol cigarettes (Ahijevych & Garrett, 2010). However, these studies also suggest that the appeal of menthol cigarettes is also based on a prior familiarity of menthol as a taste with incentive salience-"tasting like a peppermint patty" (Richter et al, 2008).…”

Section: Experiments 3: Operant Choice Testsmentioning

confidence: 99%

Effects of Nicotine on Olfactogustatory Incentives: Preference, Palatability, and Operant Choice Tests

Palmatier

Lantz

O’Brien

et al. 2013

Nicotine & Tobacco Research

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The use of additives in tobacco may capitalize on the incentive motivational properties of tastes and scents such as mint (menthol), vanilla, and strawberry. These incentives are intended to increase tobacco experimentation, but their salience may also be enhanced by the incentive amplifying effects of nicotine (NIC). The goal of the present studies was to investigate the potential interaction between the incentive amplifying effects of NIC and gustatory incentives.

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“…To accept it as such would be to very narrowly define the concept of public health harm. Rather the harm of menthol is in its masking of the harshness of tobacco smoke (22)(23)(24), its use in starter products for children (25)(26)(27)(28), its interference with quitting and staying quit (29)(30)(31)(32)(33)(34)(35)(36), and the deliberate targeting of menthol cigarettes to vulnerable populations (25,37,38). Menthol cigarettes are disproportionately target marketed to young African Americans, a particularly vulnerable segment of our society (38,39).…”

mentioning

confidence: 99%

“…Menthol masks the harshness of tobacco and provides a sensation of coolness (21), and makes low-tar cigarettes more attractive (45). The unique sensory effects of menthol, in combination with nicotine, contribute to the reinforcing effects of smoking (34).…”

mentioning

confidence: 99%

Menthol Should Not Be Given a Free Pass Based on Studies of Biomarkers of Toxicity

Clark

Gardiner

2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Exposure and toxicity studies comparing menthol and nonmenthol cigarettes have resulted in mixed results. On the basis of those results, cigarette manufacturers have concluded that there is no increased harm from the addition of menthol to cigarettes. We propose that such a narrow definition of harm is not appropriate in dealing with the issue of menthol, and its broader negative public health impact. Cancer Epidemiol Biomarkers Prev; 20(7); 1269-71. '2011 AACR.

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The Role of Menthol in Cigarettes as a Reinforcer of Smoking Behavior

Cited by 110 publications

References 34 publications

Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward

Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward

Effects of Nicotine on Olfactogustatory Incentives: Preference, Palatability, and Operant Choice Tests

Menthol Should Not Be Given a Free Pass Based on Studies of Biomarkers of Toxicity

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