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dc.contributor.advisorWinn, Philip
dc.contributor.advisorAlderson, Helen
dc.contributor.advisorBrown, Gillian R.
dc.contributor.advisorMead, Andrew
dc.contributor.authorPorter, Ailsa
dc.coverage.spatial270en
dc.date.accessioned2008-06-03T12:58:05Z
dc.date.available2008-06-03T12:58:05Z
dc.date.issued2008-06
dc.identifier.urihttp://hdl.handle.net/10023/507
dc.description.abstractThe reinforcing properties of nicotine depend partly on cholinergic projections from the pedunculopontine tegmental (PPTg) and laterodorsal tegmental (LDTg) nuclei to midbrain dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Neuronal activation was investigated using Fos expression in these areas following acute (0, 0.1, 0.4, 0.8mg/kg) or chronic systemic nicotine (0, 0.1, 0.4, 0.8, 1.0mg/kg given once per day for 5 days). We also examined co-localization of Fos expression in bNOS and TH positive neurons to determine what populations of neurons were activated by nicotine. Acute nicotine resulted in dose related Fos expression, with the biggest increase seen after 0.4mg/kg nicotine, but no co-localization occurred with bNOS in the PPTg/LDTg. Surprisingly, nicotine also failed to activate midbrain dopamine neurons. After animals were sensitized to nicotine there was a similar dose response curve in Fos expression, but the biggest increase was seen after 0.8mg/kg nicotine. Chronic nicotine, like acute, also preferentially activated non-cholinergic neurons in the LDTg and PPTg and non-dopamine neurons in the SNc and VTA. Further experiments looked at the mechanisms of Fos expression after nicotine administration. Fos expression in the LDTg/PPTg and SNc/VTA was suppressed after d-amphetamine, despite an increase in locomotor activity, suggesting that the increased Fos expression after chronic nicotine was not simply due to the locomotor activating effects of sensitized nicotine. Blocking autoreceptors in the dopaminergic midbrain by haloperidol pre-treatment did not increase Fos expression in dopamine neurons indicating that the inhibitory mechanism was not dependent on local autoreceptors. Novel methods of visualising and lesioning GABA neurons in the mesopontine tegmentum and midbrain were also examined. The data suggest that the mechanisms by which dopamine is involved in the pharmacological actions of passively administered nicotine are more complex than was first thought and that the role of non-dopamine neurons in the VTA (possibly GABA or glutamate containing) are also important.en
dc.format.extent254572175 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherUniversity of St Andrews
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subjectPedunculopontine tegmental nucleusen
dc.subjectNicotineen
dc.subjectAddictionen
dc.subjectMidbrainen
dc.subjectFosen
dc.subjectGAD expressionen
dc.subject.lccQP376.8P7
dc.subject.lcshNicotine addiction.en
dc.subject.lcshMesencephalonen
dc.subject.lcshDopaminergic mechanismsen
dc.subject.lcshCholinergic mechanismsen
dc.subject.lcshGene expressionen
dc.titleImmediate early gene expression in the mesopontine tegmentum and midbrain after acute or chronic nicotine administrationen
dc.typeThesisen
dc.contributor.sponsorMerck, Sharpe & Dohmeen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen
dc.publisher.institutionThe University of St Andrewsen


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