title: Striatal dopamine release regulation by the cholinergic properties of the smokeless tobacco, gutkha.
abstract: Tobacco products influence striatal dopamine (DA) release primarily through the actions of nicotine, an agonist of nicotinic acetylcholine receptors (nAChR). Gutkha is a smokeless tobacco product that contains not only nicotine, but also includes the habit-forming areca nut and other plant-based constituents that contribute muscarinic acetylcholine receptor (mAChR) agonists and other cholinergic agents. Thus, the net influence of the cholinergic agents in gutkha on striatal DA release is difficult to predict. This study investigated the influence of gutkha extract on evoked DA release in mouse striatal slices using fast-scan cyclic voltammetry. The potency of a given concentration of nicotine in the gutkha extract was found to be significantly lower than that of a comparable concentration of nicotine alone. Atropine, a mAChR antagonist, increased the potency of gutkha-associated nicotine; however, other experiments suggested that this was mediated in part by direct effects of atropine at nAChRs. Overall, these results suggest that the unique constituents of gutkha work together to oppose the influence of gutkha-associated nicotine on evoked striatal DA release.
authors: Brian
authors: B
authors: O'Neill
authors: §Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, United States.
authors: Dana
authors: D
authors: Lauterstein
authors: Jyoti C
authors: JC
authors: Patel
authors: §Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, United States.
authors: Judith T
authors: JT
authors: Zelikoff
authors: Margaret E
authors: ME
authors: Rice
mesh_terms: D000818:Animals; D001114:Areca; D001285:Atropine / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D046509:Tissue Culture Techniques; D014030:Tobacco, Smokeless
chemical_list: D018678:Cholinergic Agents; D010936:Plant Extracts; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D009538:Nicotine; D001285:Atropine; D004298:Dopamine
keywords: Nicotine; atropine; brain slices; dorsal striatum; fast-scan cyclic voltammetry; nAChR