Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111811
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dc.contributor.authorFurlong, T.en
dc.contributor.authorDuncan, J.en
dc.contributor.authorCorbit, L.en
dc.contributor.authorRae, C.en
dc.contributor.authorRowlands, B.en
dc.contributor.authorMaher, A.en
dc.contributor.authorNasrallah, F.en
dc.contributor.authorMilligan, C.en
dc.contributor.authorPetrou, S.en
dc.contributor.authorLawrence, A.en
dc.contributor.authorBalleine, B.en
dc.date.issued2016en
dc.identifier.citationJournal of Neurochemistry, 2016; 139(5):806-822en
dc.identifier.issn0022-3042en
dc.identifier.issn1471-4159en
dc.identifier.urihttp://hdl.handle.net/2440/111811-
dc.description.abstractToluene is a commonly abused inhalant that is easily accessible to adolescents. Despite the increasing incidence of use, our understanding of its long-term impact remains limited. Here, we used a range of techniques to examine the acute and chronic effects of toluene exposure on glutameteric and GABAergic function, and on indices of psychological function in adult rats after adolescent exposure. Metabolomics conducted on cortical tissue established that acute exposure to toluene produces alterations in cellular metabolism indicative of a glutamatergic and GABAergic profile. Similarly, in vitro electrophysiology in Xenopus oocytes found that acute toluene exposure reduced NMDA receptor signalling. Finally, in an adolescent rodent model of chronic intermittent exposure to toluene (10 000 ppm), we found that, while toluene exposure did not affect initial learning, it induced a deficit in updating that learning when response-outcome relationships were reversed or degraded in an instrumental conditioning paradigm. There were also group differences when more effort was required to obtain the reward; toluene-exposed animals were less sensitive to progressive ratio schedules and to delayed discounting. These behavioural deficits were accompanied by changes in subunit expression of both NMDA and GABA receptors in adulthood, up to 10 weeks after the final exposure to toluene in the hippocampus, prefrontal cortex and ventromedial striatum; regions with recognized roles in behavioural flexibility and decision-making. Collectively, our data suggest that exposure to toluene is sufficient to induce adaptive changes in glutamatergic and GABAergic systems and in adaptive behaviour that may underlie the deficits observed following adolescent inhalant abuse, including susceptibility to further drug-use.en
dc.description.statementofresponsibilityTeri M. Furlong, Jhodie R. Duncan, Laura H. Corbit, Caroline D. Rae, Benjamin D. Rowlands, Anthony D. Maher, Fatima A. Nasrallah, Carol J. Milligan, Steven Petrou, Andrew J. Lawrence, Bernard W. Balleineen
dc.language.isoenen
dc.publisherWileyen
dc.rights© 2016 International Society for Neurochemistryen
dc.subjectGlutamatergic dysfunction; inhalant abuse; instrumental conditioning; metabolomics; NMDA receptor; oocyteen
dc.titleToluene inhalation in adolescent rats reduces flexible behaviour in adulthood and alters glutamatergic and GABAergic signallingen
dc.typeJournal articleen
dc.identifier.rmid0030084274en
dc.identifier.doi10.1111/jnc.13858en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1079561en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1020737en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/630516en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/568767en
dc.relation.granthttp://purl.org/au-research/grants/arc/FL0992409en
dc.relation.granthttp://purl.org/au-research/grants/arc/DP110100379en
dc.relation.granthttp://purl.org/au-research/grants/arc/FT100100235en
dc.identifier.pubid401438-
pubs.library.collectionMedicine publicationsen
pubs.library.teamDS14en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Medicine publications

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