The underlying mechanism of morphine tolerance remains unclear. EphB2 regulates synaptic efficiency with respect to learning and memory. Previously, we demonstrated that loss of EphB2 significantly accelerates the rate of morphine tolerance and alters behavioural responses to morphine following tolerance. However, EphB2 null mice exhibit no significant alteration in their metabolism of morphine compared to littermate controls, or altered mu opioid receptor expression levels within the spinal cord or brain compared to littermate controls. Therefore, we investigated whether loss of EphB2 alters learned responsiveness to morphine through modification of hippocampal function. Interestingly, results indicate that electrolytic lesions of the dorsal hippocampus of wild-type mice display similar behavioural responses seen in EphB2 null mice compared to sham operated controls. These findings suggest that loss of EphB2 function within the hippocampus is a critical feature in mediating morphine-dependent tolerance, and suggests a novel role for EphB2 receptor signaling in opiate-dependent learning.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33231 |
| Date | 20 November 2012 |
| Creators | Huroy, Sofia |
| Contributors | Henderson, Jeffrey T. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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