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dc.contributor.advisorSmith, Paul F.
dc.contributor.advisorZheng, Yiwen
dc.contributor.advisorDarlington, Cynthia L.
dc.contributor.authorBaek, Jean-Ha
dc.date.available2011-05-05T23:36:06Z
dc.date.copyright2011
dc.identifier.citationBaek, J.-H. (2011). Changes in the Endocannabinoid system in the Brain Following Bilateral Vestibular Damage (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/1689en
dc.identifier.urihttp://hdl.handle.net/10523/1689
dc.description.abstractNumerous studies have shown that bilateral vestibular deafferentation (BVD) results in spatial memory deficits and hippocampal dysfunction in rats and humans. These deficits appear to be long-lasting, suggesting long-term adverse effects on the hippocampus, a brain region known for its role in learning and memory. Interestingly, the endocannabinoid system has also been demonstrated to have a role in modulating hippocampal synaptic neurotransmission and cognitive function. Not only are the cannabinoid receptors highly expressed in the hippocampus, the activation of these receptors by either the endogenous ligands (that is, endocannabinoids) or exogenous cannabinoid drugs results in the impairment in a variety of learning and memory tasks. As it has been demonstrated that vestibular damage causes learning and memory deficits and that the endocannabinoid system is critically involved in the mechanism of learning and memory, the aim of this study was to investigate whether the hippocampal endocannabinoid system plays a role in the functional changes seen after vestibular damage. By manipulating the available cues in the foraging task, 14 months post-BVD animals were unable to use available visual cues and execute piloting as their navigating strategy. In addition, their spatial navigation ability became worse in darkness. Importantly, it appears that these cognitive impairments due to the vestibular damage are highly likely to be permanent. It was expected that the administration of the cannabinoid receptor agonist would exacerbate the observed spatial memory deficits in the BVD animals as it has been shown to have disruptive effects on spatial learning and memory in both animals and humans. In the present study, it was found that 1 mg/kg WIN55212-2 (WIN), a cannabinoid receptor agonist, was sufficient to produce object recognition memory impairments in adult rats. However, when the same drug was given to both the BVD and the sham animals, its effect on spatial memory was complex. It was shown that WIN, at 2 mg/kg, significantly improved the performance in the dark in BVD, but not sham animals, suggesting that BVD might have resulted in changes in the brain’s endocannabinoid system. However, the pre-treatment with AM251, a cannabinoid receptor inverse agonist, further indicated the complexity of involvement of the endocannabinoid system in the cognitive deficits following BVD. Since cannabinoid cannabinoid 1 (CB1) receptors are well known to regulate synaptic plasticity in the hippocampus, whether BVD resulted in changes in CB1 receptor expression and affinity in the rat hippocampus at 1, 3 and 7 days post-surgery was investigated, using a combination of western blotting and radioligand binding. It was found that the CB1 receptor down-regulates in the CA3 region of the hippocampus following BVD, but with no changes in the affinity of the CB1 receptor for WIN. Overall, the results from the present study suggest that cognitive deficits following BVD may be permanent and provide some preliminary evidence for future research on the role of the endocannabinoid system in the observed cognitive deficits following vestibular damage in order to further elucidate the potential mechanism(s) that may underlie this impairment.
dc.format.mimetypeapplication/pdf
dc.language.isoen_NZ
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectVestibular damage
dc.subjectEndocannabinoid System
dc.subjectCannabinoid drugs
dc.subjectCognitive deficits
dc.subjectHippocampus
dc.titleChanges in the Endocannabinoid system in the Brain Following Bilateral Vestibular Damage
dc.typeThesis
dc.date.updated2011-05-04T13:22:43Z
thesis.degree.disciplinePharmacology & Toxicology
thesis.degree.nameDoctor of Philosophy
thesis.degree.grantorUniversity of Otago
thesis.degree.levelDoctoral Theses
otago.openaccessOpen
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