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dc.contributor.authorFalon, Jessica
dc.date.accessioned2019-07-29
dc.date.available2019-07-29
dc.date.issued2019-04-12
dc.identifier.urihttp://hdl.handle.net/2123/20801
dc.description.abstractPain places a great burden upon society, and a better understanding of pain circuitry will be critical to developing new therapies. Of interest is the connection between the medial nucleus of the central amygdala (CeM) and periaqueductal gray (PAG), due to its role in producing analgesia. Opioid and cannabinoid analgesics act upon this pathway, though their specific sites of action within amygdala pain circuitry has not been fully determined. Therefore, the present study aimed to address this using tract tracing and whole cell patch clamp electrophysiology. Retrograde tracer was injected into the rat PAG, and the effects of opioids and cannabinoids on inhibitory inputs to labelled and unidentified CeM neurons was recorded. Notably, while DAMGO reduced inhibitory input to the CeM in both unidentified and labelled projection neurons, deltorphin inhibited inputs to unidentified neurons alone, and U69593 to only projection neurons. DHPG also produced short-term inhibition of inhibitory inputs to CeM neurons, which was abolished by AM251 in unidentified but not labelled neurons. This inhibition was associated with an extended recovery time, which was reduced by AM251 in both populations. These findings suggest that pain processing amygdala circuitry is differentially modulated by opioid receptor agonists. DHPG also modulates this circuitry, however in projection neurons, short-term inhibition seemed to be cannabinoid-independent and longer-term inhibition to be cannabinoid-dependent, potentially indicative of cannabinoid-dependent long-term depression (LTD). Overall, this study is the first to electrophysiologically demonstrate a role for cannabinoids in modulating inputs to PAG-projecting CeM neurons, as well as for κ-receptor agonists in preferentially inhibiting these inputs. This broadens our understanding of how these analgesics interact with pain circuitry via the amygdala, and may lead to more successful manipulation of this pathway to effectively manage pain.en_AU
dc.publisherUniversity of Sydneyen_AU
dc.publisherFaculty of Medicine and Healthen_AU
dc.publisherDiscipline of Pharmacologyen_AU
dc.publisherNorthern Clinical Schoolen_AU
dc.rightsThe author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.en_AU
dc.subjectpainen_AU
dc.subjectamygdalaen_AU
dc.subjectopoiden_AU
dc.subjectcannabinoiden_AU
dc.titleCellular Characterisation of Endogenous Analgesic Systemsen_AU
dc.typeMasters Thesisen_AU
dc.type.pubtypeMaster of Philosophy M.Philen_AU
dc.description.disclaimerAccess is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.en_AU


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