In the field of drug addiction, relapse back to drug seeking and taking is the major unmet clinical need. The rate of relapse back to drug-taking is ~70-80% within a year of drug abstinence. Gaining a better understanding of the prolonged neuronal changes that have taken place during drug addiction may lead to the design of better anti-relapse therapies. It is now widely believed that one component of drug addiction is by aberrant learning and memory processes. To study this, we investigated synaptic changes caused by the development of drug-seeking behaviour in C57BL/6J mice. Mice were treated either with non-contingent morphine or trained to exhibit drug-seeking behaviour following morphine-induced conditioned place preference (CPP) training, hippocampal slices were taken from these animals and synaptic changes examined at the CA3-CA1 synapse using electrophysiological methods. Mice that underwent morphine CPP were demonstrated to exhibit a significant preference for the morphine paired compartment before ex vivo electrophysiological analysis. Using field recordings, both non-contingent morphine and morphine CPP treatments resulted in a reduced ability to undergo stimulus-induced LTP compared to their respective controls. Whole cell patch clamp was then utilised to further investigate these effects. Non-contingent morphine treatment resulted in both pre- and post-synaptic changes with an increased AMPA:NMDA receptor ratio, concurrent increases in cell size, and reductions in the release probability of both glutamate and GABA. Morphine CPP treatment resulted in a more variable increase in AMPA:NMDA receptor ratio (presumably by the same mechanism but in a more specific group of neurones) and GABA release probability was also decreased. There were no detected increases in cell size however, or any detected changes in glutamate release probability. These findings therefore reveal a set of synaptic adaptations in the hippocampus unique to morphine-induced behavioural change, and may provide targets for future intervention in drug addiction.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:607146 |
| Date | January 2013 |
| Creators | Rigby, Peter Thomas |
| Contributors | Bailey, Christopher |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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