Dissertation
The involvement of matrix metalloproteinases in nicotine conditioned place preference in adolescent female rats
Washington State University
Doctor of Philosophy (PhD), Washington State University
12/2009
DOI:
https://doi.org/10.7273/000005935
Abstract
The process of learning new information or modifying existing information requires synaptic plasticity in the brain. In order for these plasticity events to occur, the extracellular matrix (ECM) is reconfigured and reorganized by their primary modulators-- the matrix metalloproteinases (MMP). MMPs are a class of proteinases that are known to be involved in the learning and memory process by modulating synaptic plasticity. Our hypothesis is that MMP dependent synaptic restructuring takes place during the acquisition of drug dependent learning. We used a nicotine conditioned place preference (CPP) model to understand the underlying synaptic events that drives drug preference. There has been some debate regarding the ability of nicotine to elicit CPP in rats. Therefore the goal of the studies described in chapter 2 was to first establish that nicotine induced CPP. Our results show that nicotine produces robust, reproducible CPP at 0.03mg/kg dose using a 5 day drug administration protocol. We also observed that higher doses of nicotine produced conditioned place aversion. In chapter 3 we noted changes in the activity of MMPs - 2, 3, and 9 in the hippocampus and prefrontal cortex after conditioning. Inhibition of MMPs during nicotine conditioning interfered with the development of CPP. Elevation in MMP-3, but not MMP-2 and MMP-9 expression, accompanied re-activation of previously learnt drug related memory in both the hippocampus and the prefrontal cortex. Changes in the activity of cortactin, an actin bound cytoskeletal marker protein, were also observed during the acquisition of CPP but not following re-exposure to the drug context. These results suggest that MMPs - 2, 3, and 9 are involved in facilitating intracellular and extracellular events required for synaptic plasticity and memory consolidation while MMP-3 is uniquely involved in the reconsolidation process.
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Details
- Title
- The involvement of matrix metalloproteinases in nicotine conditioned place preference in adolescent female rats
- Creators
- Reka Natarajan
- Contributors
- Joseph W. Harding (Chair)John William Wright (Committee Member) - Washington State University, Department of PsychologyBarbara Sorg Ingermann (Committee Member) - Washington State University, Department of Integrative Physiology and NeuroscienceMichael Varnum (Committee Member) - Washington State University, Department of Integrative Physiology and NeuroscienceHeiko Jansen (Committee Member) - Washington State University, Department of Integrative Physiology and Neuroscience
- Awarding Institution
- Washington State University
- Academic Unit
- Program in Neuroscience
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 122
- Identifiers
- 99901055132301842
- Language
- English
- Resource Type
- Dissertation