The role of microglia in addiction in a mouse model

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2013-11-22

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Abstract

Microglia, the immune cells of the brain, have traditionally been studied solely for their immunological functions. Here, we suggest a novel involvement of microglia in the development and maintenance of addiction to opioids and other drugs of abuse. In response to drugs of abuse such as morphine, microglia shift to an activated state that involves upregulated release of cytokines and chemokines, the small cell-signaling protein molecules of the immune system. Previous work in our laboratory has demonstrated that increased expression of the anti-inflammatory cytokine, IL-10, inhibits morphine-induced glial pro-inflammation within the nucleus accumbens (NAcc), and prevents morphine relapse. We therefore seek to translate these findings to a mouse model in order to further our research through transgenic manipulations. Through this project, we verify the viability of a mouse model through the elucidation of the molecular response to morphine administration in mice. We identify the optimal time point (e.g. 60 minutes) for identifying the molecular profile of morphine administration due to optimal morphine activity. Additionally, important patterns of cytokine expression observed in rat studies involving toll-like-receptor (TLR)4, CCL4, and neuronal fractalkine, are reproduced in mice. TLR4 has been implicated as a major player in addiction; therefore, we also tested the learning and memory abilities of a TLR4 knockout (KO) mouse through the well-established fear-conditioning paradigm since addiction is closely related to cognition. TLR4 KO behavior analysis shows no significant difference in fear conditioning between male TLR4 heterozygote (HET) and KO mice. Densitometry analysis also shows no difference in microglia density in these animals. Collectively, these results confirm the viability of a mouse model in continuing our research, investigating the role of microglia in addiction.

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Ngan, Emily (2013). The role of microglia in addiction in a mouse model. Honors thesis, Duke University. Retrieved from https://hdl.handle.net/10161/8107.


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