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Menthol facilitates the intravenous self-administration of nicotine in rats.

ABSTRACT: Menthol is preferred by ~25% of smokers and is the most common flavoring additive in tobacco and electronic cigarettes. Although some clinical studies have suggested that menthol facilitates the initiation of smoking and enhances the dependence on nicotine, many controversies remain. Using licking as the operant behavior, we found that adolescent rats self-administering nicotine (30?g/kg/infusion, free base, i.v.) with contingent oral menthol (60?l, 0.01% w/v) obtained significantly more infusions than rats receiving a vehicle cue or rats self-administering i.v. saline with a menthol cue. Rats yoked to their menthol-nicotine masters emitted significantly fewer licks on the active spouts, indicating that contingent pairing between nicotine and menthol is required for sustained nicotine intake. Rats that self-administered nicotine with a menthol cue also exhibited a long-lasting extinction burst and robust reinstatement behavior, neither of which were observed in rats that self-administered saline with a menthol cue. The cooling sensation of menthol is induced by activating the transient receptor potential M8 (TRPM8) channel. When WS-23, an odorless agonist of the TRPM8 channel, was used as a contingent cue for nicotine, the rats obtained a similar number of nicotine infusions as the rats that were provided a menthol cue and exhibited a strong preference for the active spout. In contrast, highly appetitive taste and odor cues failed to support nicotine self-administration. These data indicated that menthol, likely by inducing a cooling sensation, becomes a potent conditioned reinforcer when it is contingently delivered with nicotine. Together, these results provide a key behavioral mechanism by which menthol promotes the use of tobacco products or electronic cigarettes.

SUBMITTER: Wang T

PROVIDER: S-EPMC4267270 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Menthol facilitates the intravenous self-administration of nicotine in rats.

Wang Tengfei T Wang Bin B Chen Hao H

Frontiers in behavioral neuroscience 20141216

Menthol is preferred by ~25% of smokers and is the most common flavoring additive in tobacco and electronic cigarettes. Although some clinical studies have suggested that menthol facilitates the initiation of smoking and enhances the dependence on nicotine, many controversies remain. Using licking as the operant behavior, we found that adolescent rats self-administering nicotine (30μg/kg/infusion, free base, i.v.) with contingent oral menthol (60μl, 0.01% w/v) obtained significantly more infusio ...[more]

PMID: 25566005

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Project description:INTRODUCTION:Nicotine can robustly increase responding for conditioned reinforcers (CRs), stimuli that acquire reinforcing properties based on association with primary reinforcers. Menthol and licorice are tobacco flavoring agents also found in sweet foods (eg, candy and ice cream), making them putative CRs before they are consumed in tobacco. We sought to determine if intravenous self-administration (IVSA) of nicotine was enhanced by the inclusion of oral tobacco flavor CRs. METHODS:Menthol (160 or 320 µM) or licorice root extract (0.1% or 1%) were established as CRs (paired with 20% sucrose) or "neutral" stimuli (paired with water) in separate groups. During subsequent IVSA tests, nicotine was delivered in conjunction with oral presentations of the CR. RESULTS:In experiment 1, a menthol CR significantly shifted the peak nicotine dose from 15 µg/kg/infusion (Neutral group) to 3.25 µg/kg/infusion (CR group). In experiment 2, a menthol CR significantly increased operant licks for nicotine (3 µg/kg/infusion) relative to control groups. In experiment 3, both licorice and menthol CRs significantly increased operant licks for nicotine (7.5 µg/kg/infusion) relative to an "inactive" sipper. The licorice CR increased nicotine IVSA in proportion to the strength of the flavor, but both menthol concentrations increased nicotine IVSA to a similar extent. CONCLUSION:Tobacco flavor additives with conditioned reinforcing properties promote acquisition of nicotine self-administration at low unit doses and may have robust impact on tobacco consumption when nicotine yield is low. IMPLICATIONS:Tobacco flavor additives are found in rewarding foods (eg, ice cream) and gain palatability based on associations with primary rewards (eg, sugar) making them "conditioned reinforcers." Nicotine increases the motivation for flavor conditioned reinforcers and the present studies show that tobacco flavor additives can interact with nicotine to promote more nicotine self-administration. The interaction between flavors additives and nicotine may promote nicotine exposure and subsequently dependence.

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Menthol facilitates the intravenous self-administration of nicotine in rats.

Publications

Menthol facilitates the intravenous self-administration of nicotine in rats.

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