Learning and memory mechanisms that are normally related to natural rewards, such as long-term potentiation (LTP) and depression (LTD), may be usurped by the voluntary intake of drugs of abuse. The maladaptive behaviour that characterizes addiction is thought to arise from persistent changes in excitatory synaptic function in brain reward circuits. The oval region of the dorsal bed nucleus of the stria terminalis (ovBST) is one such region susceptible to drug-induced synaptic remodeling and is implicated in drug-driven behaviors, reinforcement and stress-induced relapse to drug-seeking. Using whole-cell voltage clamp recordings of ovBST neurons in brain slices prepared from adult Long-Evans rats, we demonstrated an unrestrained increase in AMPAR-mediated excitatory transmission with maintenance of cocaine self-administration. This is unlike self-administration of a natural reward, in which we observed an enhancement and then decline of AMPAR-mediated transmission with continued intake. Additionally, we demonstrate impairment in NMDAR-mediated LTD in ovBST neurons with cocaine self-administration. This impairment may be due to resilient GluN2B-containing NMDARs, as application of a GluN2B-antagonist rescued impaired LTD. Based on models of NMDAR-mediated bidirectional plasticity we suggest that a drug-induced de-regulation between GluN2A and GluN2B subunits impairs LTD, which may underlie the enhancement AMPAR-mediated transmission. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2012-05-31 09:46:39.312
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/7321 |
| Date | 17 July 2012 |
| Creators | DEBACKER, JULIAN |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner. |
| Relation | Canadian theses |
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