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dc.contributor.authorNimitvilai, Sudarat
dc.contributor.authorYou, Chang
dc.contributor.authorArora, Devinder
dc.contributor.authorA. McElvain, Maureen
dc.contributor.authorVandegrift, Bertha J.
dc.contributor.authorS. Brodie, Mark
dc.contributor.authorWoodward, John J.
dc.date.accessioned2018-01-22T04:51:19Z
dc.date.available2018-01-22T04:51:19Z
dc.date.issued2016
dc.identifier.issn1662-453Xen_US
dc.identifier.doi10.3389/fnins.2016.00434en_US
dc.identifier.urihttp://hdl.handle.net/10072/143146
dc.description.abstractDrugs of abuse increase the activity of dopaminergic neurons of the ventral tegmental area (VTA), and output from the VTA is critical for both natural and drug-induced reward and reinforcement. Ethanol and the abused inhalant toluene both enhance VTA neuronal firing, but the mechanisms of this effect is not fully known. In this study, we used extracellular recordings to compare the actions of toluene and ethanol on DA VTA neurons. Both ethanol and toluene increased the firing rate of DA neurons, although toluene was ~100 times more potent than ethanol. The mixed ion channel blocker quinine (100 μM) blocked the increases in firing produced by ethanol and toluene, indicating some similarity in mechanisms of excitation. A mixture of antagonists of GABA and cholinergic receptors did not prevent toluene-induced or ethanol-induced excitation, and toluene-induced excitation was not altered by co-administration of ethanol, suggesting independent mechanisms of excitation for ethanol and toluene. Concurrent blockade of NMDA, AMPA, and metabotropic glutamate receptors enhanced the excitatory effect of toluene while having no significant effect on ethanol excitation. Nicotine increased firing of DA VTA neurons, and this was blocked by the nicotinic antagonist mecamylamine (1 μM). Mecamylamine did not alter ethanol or toluene excitation of firing but the muscarinic antagonist atropine (5 μM) or a combination of GABA antagonists (bicuculline and CGP35348, 10 μM each) reduced toluene-induced excitation without affecting ethanol excitation. The Ih current blocker ZD7288 abolished the excitatory effect of toluene but unlike the block of ethanol excitation, the effect of ZD7288 was not reversed by the GIRK channel blocker barium, but was reversed by GABA antagonists. These results demonstrate that the excitatory effects of ethanol and toluene have some similarity, such as block by quinine and ZD7288, but also indicate that there are important differences between these two drugs in their modulation by glutamatergic, cholinergic, and GABAergic receptors. These findings provide important information regarding the actions of abused inhalants on central reward pathways, and suggest that regulation of the activation of central dopamine pathways by ethanol and toluene partially overlap.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherFrontiers Research Foundationen_US
dc.relation.ispartofpagefrom434-1en_US
dc.relation.ispartofpageto434-12en_US
dc.relation.ispartofjournalFrontiers in Neuroscienceen_US
dc.relation.ispartofvolume10en_US
dc.subject.fieldofresearchNeurosciences not elsewhere classifieden_US
dc.subject.fieldofresearchcode110999en_US
dc.titleDifferential Effects of Toluene and Ethanol on Dopaminergic Neurons of the Ventral Tegmental Areaen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/en_US
dc.description.versionPublisheden_US
gro.rights.copyright© 2016 Nimitvilai, You, Arora, McElvain, Vandegrift, Brodie and Woodward. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
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