title: Nicotine activates TRPM5-dependent and independent taste pathways.
abstract: The orosensory responses elicited by nicotine are relevant for the development and maintenance of addiction to tobacco products. However, although nicotine is described as bitter tasting, the molecular and neural substrates encoding the taste of nicotine are unclear. Here, rats and mice were used to determine whether nicotine activates peripheral and central taste pathways via TRPM5-dependent mechanisms, which are essential for responses to other bitter tastants such as quinine, and/or via nicotinic acetylcholine receptors (nAChRs). When compared with wild-type mice, Trpm5(-/-) mice had reduced, but not abolished, chorda tympani (CT) responses to nicotine. In both genotypes, lingual application of mecamylamine, a nAChR-antagonist, inhibited CT nerve responses to nicotine and reduced behavioral responses of aversion to this stimulus. In accordance with these findings, rats were shown to discriminate between nicotine and quinine presented at intensity-paired concentrations. Moreover, rat gustatory cortex (GC) neural ensemble activity could also discriminate between these two bitter tastants. Mecamylamine reduced both behavioral and GC neural discrimination between nicotine and quinine. In summary, nicotine elicits taste responses through peripheral TRPM5-dependent pathways, common to other bitter tastants, and nAChR-dependent and TRPM5-independent pathways, thus creating a unique sensory representation that contributes to the sensory experience of tobacco products.
authors.affiliation: Instituto de Histologia e Embriologia, Faculdade de Medicina and Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-319 Porto, Portugal.
authors.forename: Albino J
authors.initials: AJ
authors.lastname: Oliveira-Maia
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Stapleton-Kotloski
authors.forename: Vijay
authors.initials: V
authors.lastname: Lyall
authors.forename: Tam-Hao T
authors.initials: TH
authors.lastname: Phan
authors.forename: Shobha
authors.initials: S
authors.lastname: Mummalaneni
authors.forename: Pamela
authors.initials: P
authors.lastname: Melone
authors.forename: John A
authors.initials: JA
authors.lastname: Desimone
authors.forename: Miguel A L
authors.initials: MA
authors.lastname: Nicolelis
authors.forename: Sidney A
authors.initials: SA
authors.lastname: Simon
mesh_terms: D000818:Animals; D004566:Electrodes; D008464:Mecamylamine / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050053:TRPM Cation Channels / Q000502:physiology*; D013649:Taste / Q000187:drug effects* / Q000502:physiology
chemical_list: D018733:Nicotinic Antagonists; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse; D008464:Mecamylamine; D009538:Nicotine; D011803:Quinine