Menthol Stereoisomers Exhibit Different Effects on α4β2 nAChR Upregulation and Dopamine Neuron Spontaneous Firing.

ABSTRACT: Menthol contributes to poor cessation rates among smokers, in part because menthol enhances nicotine reward and reinforcement. Mentholated tobacco products contain (-)-menthol and (+)-menthol, in varying proportions. We examined these two menthol stereoisomers for their ability to upregulate α4β2 nAChRs and to alter dopamine neuron firing frequency using long-term, low-dose (≤500 nm) exposure that is pharmacologically relevant to smoking. We found that (-)-menthol upregulates α4β2 nAChRs while (+)-menthol does not. We also found that (-)-menthol decreases dopamine neuron baseline firing and dopamine neuron excitability, while (+)-menthol exhibits no effect. We then examined both stereoisomers for their ability to inhibit α4β2 nAChR function at higher concentrations (>10 µm) using the Xenop

SUBMITTER: Henderson BJ 

PROVIDER: S-EPMC6325563 | biostudies-literature | 2018 Nov-Dec

REPOSITORIES: biostudies-literature