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Dissertation
THE ROLE OF PERINEURONAL NETS AND KETAMINE IN COCAINE-ASSOCIATED MEMORY
Washington State University
Doctor of Philosophy (PhD), Washington State University
07/2024
DOI:
https://doi.org/10.7273/000007045
Abstract
Strong cocaine-associated memories contribute to relapse. These memories are persistent and are formed through repeated drug-cue associations that undergo reconsolidation. Reconsolidation is a memory maintenance process that is initiated when a memory is retrieved, usually by drug-associated reminders. This process can be strategically disrupted to diminish drug-associated memories. Cocaine-associated cues trigger responses in the prefrontal cortex (PFC), a critical hub that forms well- established connections with key brain regions associated with reward and drives cocaine seeking behavior. The medial PFC (mPFC) is highly responsive to cocaine-associated stimuli. The work outlined in this dissertation describes the role of the mPFC in cocaine-associated memory and reinstatement in rats using cocaine conditioned place preference and self-administration models. First, this dissertation outlines important background to provide a basic understanding of the processes in which cocaine forms persistent memories that drive relapse, ranging from its history to cellular processes to current methods for reducing relapse. This work then describes rapid and dynamic changes in mPFC GABAergic parvalbumin (PV) interneurons and their surrounding mesh-like structures, perineuronal nets (PNNs), following a cocaine memory retrieval. Then, the impact of mPFC enzymatic PNN degradation on cocaine-induced reinstatement and changes in mPFC PNN-surrounded PV cells are identified. Lastly, ketamine is used to impair reconsolidation of robust cocaine self-administration memories and reduce cue-reinstatement in rats. The impact of ketamine on mPFC PNNs and PV is then evaluated for its contribution to cue-reinstatement. Overall, this work finds that cocaine reminders are sufficient to induce rapid and dynamic alterations in PV cells that are surrounded by PNNs. Furthermore, in the absence of PNNs, PV neuron activity and expression is altered after cocaine-induced reinstatement. Finally, using a more translational approach, a single subanesthetic dose of ketamine remarkably and robustly reduces cocaine seeking behavior in our model of cocaine-self administration.
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Details
- Title
- THE ROLE OF PERINEURONAL NETS AND KETAMINE IN COCAINE-ASSOCIATED MEMORY
- Creators
- Angela E. Gonzalez
- Contributors
- Barbara A Sorg (Co-Chair)Michael M Morgan (Co-Chair)Rita A Fuchs Lokensgard (Committee Member)Ryan J McLaughlin (Committee Member)Shaban S Demirel (Committee Member)
- 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
- 239
- Identifiers
- 99901152338201842
- Language
- English
- Resource Type
- Dissertation