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dc.contributor.advisorFrench, Edward D.en_US
dc.contributor.authorSandoval, Karin
dc.creatorSandoval, Karinen_US
dc.date.accessioned2013-04-11T09:22:53Z
dc.date.available2013-04-11T09:22:53Z
dc.date.issued2004en_US
dc.identifier.urihttp://hdl.handle.net/10150/280646
dc.description.abstractThis dissertation represents some of the first work to investigate how acute and chronic nicotine treatment affects the in vivo electrophysiological responses of mouse ventral tegmental area (VTA) dopamine neurons, behavior, and the involvement of nicotinic acetylcholine receptors (nAChRs). We found that when mice were given an initial dose of 8μg/kg intravenous nicotine and the dose increased incrementally (16μg/kg, 32μg/kg, 64μg/kg, 128μg/kg); nicotine had no effect on VTA dopamine neuronal firing, even when the individual dose reached 256 μg/kg nicotine. However, if a higher initial dose of acute nicotine (0.1mg/kg IV doses) was administered, a dose self-administered by mice (Stolerman et al, 1999), nicotine inhibited VTA dopamine neuronal firing, with the inhibitory effect desensitizing with subsequent doses of nicotine. The inhibitory effect of acute nicotine on VTA dopamine neuronal firing and locomotion was blocked by the non-specific nAChR antagonist mecamylamine, demonstrating that the locomotor and in vivo electrophysiological responses to acute nicotine are mediated through nAChRs. Furthermore, α4*β2* nAChRs were found to mediate the inhibitory effect of acute nicotine with respect to locomotion and in vivo electrophysiological responses of VTA dopamine neurons, as nicotine's depressant effects were blocked in mice pretreated with dihydro-beta-erythroidine (DHβE). The α7 nAChRs appear to play no role in the inhibitory effects of acute nicotine on locomotion as methyllycaconitine (doses up to 10mg/kg), had no effect on nicotine-induced hypolocomotion. Chronic nicotine treatment for 10 days resulted in electrophysiological (in vivo) and behavioral tolerance to the effects of nicotine in mice. In mice chronically treated with nicotine, the VTA dopamine neuronal response to nicotine was significantly reduced. Nicotine's depressant effects on body temperature and locomotion were also significantly reduced after 10 days of nicotine treatment. Furthermore, the ICR mouse strain was found to be nicotine-sensitive, as nicotine inhibited locomotor activity in a manner more similar to the DBA/2 strain, a standard nicotine-sensitive strain of mouse as compared to the C3H/HeJ strain, a standard nicotine-resistant strain. The ICR mouse was also found to be spontaneously more active than the DBA/2 and C3H/HeJ strain.
dc.language.isoen_USen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectBiology, Neuroscience.en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.titleAn assessment of nicotine's effects on behavioral and in vivo electrophysiological responses of ventral tegmental area dopamine neurons in the mouseen_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.identifier.proquest3145122en_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology & Toxicologyen_US
thesis.degree.namePh.D.en_US
dc.identifier.bibrecord.b47210308en_US
refterms.dateFOA2018-06-25T15:59:42Z
html.description.abstractThis dissertation represents some of the first work to investigate how acute and chronic nicotine treatment affects the in vivo electrophysiological responses of mouse ventral tegmental area (VTA) dopamine neurons, behavior, and the involvement of nicotinic acetylcholine receptors (nAChRs). We found that when mice were given an initial dose of 8μg/kg intravenous nicotine and the dose increased incrementally (16μg/kg, 32μg/kg, 64μg/kg, 128μg/kg); nicotine had no effect on VTA dopamine neuronal firing, even when the individual dose reached 256 μg/kg nicotine. However, if a higher initial dose of acute nicotine (0.1mg/kg IV doses) was administered, a dose self-administered by mice (Stolerman et al, 1999), nicotine inhibited VTA dopamine neuronal firing, with the inhibitory effect desensitizing with subsequent doses of nicotine. The inhibitory effect of acute nicotine on VTA dopamine neuronal firing and locomotion was blocked by the non-specific nAChR antagonist mecamylamine, demonstrating that the locomotor and in vivo electrophysiological responses to acute nicotine are mediated through nAChRs. Furthermore, α4*β2* nAChRs were found to mediate the inhibitory effect of acute nicotine with respect to locomotion and in vivo electrophysiological responses of VTA dopamine neurons, as nicotine's depressant effects were blocked in mice pretreated with dihydro-beta-erythroidine (DHβE). The α7 nAChRs appear to play no role in the inhibitory effects of acute nicotine on locomotion as methyllycaconitine (doses up to 10mg/kg), had no effect on nicotine-induced hypolocomotion. Chronic nicotine treatment for 10 days resulted in electrophysiological (in vivo) and behavioral tolerance to the effects of nicotine in mice. In mice chronically treated with nicotine, the VTA dopamine neuronal response to nicotine was significantly reduced. Nicotine's depressant effects on body temperature and locomotion were also significantly reduced after 10 days of nicotine treatment. Furthermore, the ICR mouse strain was found to be nicotine-sensitive, as nicotine inhibited locomotor activity in a manner more similar to the DBA/2 strain, a standard nicotine-sensitive strain of mouse as compared to the C3H/HeJ strain, a standard nicotine-resistant strain. The ICR mouse was also found to be spontaneously more active than the DBA/2 and C3H/HeJ strain.


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