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dc.contributor.authorMoreira da Silva Santos, Andreia
dc.contributor.authorKelly, John P.
dc.contributor.authorDockery, Peter
dc.contributor.authorDoyle, Karen M.
dc.date.accessioned2020-01-24T11:10:32Z
dc.date.available2020-01-24T11:10:32Z
dc.date.issued2018-10-05
dc.identifier.citationMoreira da Silva Santos, Andreia, Kelly, John P., Dockery, Peter, & Doyle, Karen M. (2019). Effect of a binge-like dosing regimen of methamphetamine on dopamine levels and tyrosine hydroxylase expressing neurons in the rat brain. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 89, 303-309. doi: https://doi.org/10.1016/j.pnpbp.2018.10.003en_IE
dc.identifier.issn1878-4216
dc.identifier.urihttp://hdl.handle.net/10379/15733
dc.description.abstractMethamphetamine, an amphetamine derivative, is a powerful psychomotor stimulant and commonly used drug of abuse. This study examined the effect of binge-like methamphetamine (MA) dosing (4 x 4 mg/kg, s.c., 2 h apart) on regional dopamine and dopaminergic metabolite levels in rat brain at a range of early time points after final dose (2-48 h). Body temperature was elevated when measured 2 h after the last dose. MA increased dopamine levels in the frontal cortex 2 and 24 h after the last dose. The dopamine level was also increased in the amygdala at 24 h. No change was observed in the striatum at any time point, but levels of the dopamine metabolite DOPAC were markedly reduced at 24 and 48 h. Tyrosine hydroxylase expression is induced downstream of dopamine activity, and it is the rate limiting enzyme in dopamine synthesis. The effect of MA binge-like dosing on the volume of tyrosine hydroxylase containing cell bodies and the area fraction of tyrosine hydroxylase containing fibres was also assessed. MA increased the area fraction of tyrosine hydroxylase fibres in the frontal cortex and reduced the volume of tyrosine hydroxylase containing cell bodies 2 h after last dose in the ventral segmental area and the substantia nigra. An increase in cell body volume in the substantia nigra was observed 48 h after treatment. These findings collectively highlight the importance of the dopaminergic system in methamphetamine induced effects, identify the frontal cortex, amygdala and striatum as key regions that undergo early changes in response to binge-like methamphetamine dosing and provide evidence of time-dependent effects on the cell bodies and fibres of tyrosine hydroxylase expressing neurons.en_IE
dc.description.sponsorshipThis research was funded by a College of Science Scholarship, National University of Ireland, Galway. The authors acknowledge the facilities and scientific and technical assistance of the Centre for Microscopy & Imaging at the National University of Ireland Galway (www.imaging.nuigalway.ie), a facility that is funded by NUI, Galway and the Irish Government's Programme for Research in Third Level Institutions, Cycles 4 and 5, National Development Plan 2007-2013.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofProgress In Neuro-Psychopharmacology & Biological Psychiatryen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectMethamphetamineen_IE
dc.subjectDopamineen_IE
dc.subjectDopamine metabolitesen_IE
dc.subjectTyrosine hydroxylaseen_IE
dc.subjectHyperthermiaen_IE
dc.subjectMET-ENKEPHALIN SYSTEMSen_IE
dc.subjectSTRIATAL DOPAMINEen_IE
dc.subjectINDUCED HYPERTHERMIAen_IE
dc.subjectNITRIC-OXIDEen_IE
dc.subjectCELL-DEATHen_IE
dc.subjectNEUROTOXICITYen_IE
dc.subjectINCREASESen_IE
dc.subjectRELEASEen_IE
dc.subjectAMPHETAMINEen_IE
dc.subjectDEPLETIONen_IE
dc.titleEffect of a binge-like dosing regimen of methamphetamine on dopamine levels and tyrosine hydroxylase expressing neurons in the rat brainen_IE
dc.typeArticleen_IE
dc.date.updated2020-01-24T09:15:29Z
dc.identifier.doi10.1016/j.pnpbp.2018.10.003
dc.local.publishedsourcehttps://doi.org/10.1016/j.pnpbp.2018.10.003en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderCollege of Science, National University of Ireland, Galwayen_IE
dc.internal.rssid15459144
dc.local.contactKaren Doyle, Dept. Of Physiology, Human Biology Building, Nui Galway. 3665 Email: karen.doyle@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
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