Full metadata
Title
Overexpression of MicroRNA-495 and its Effects on Cocaine Addiction
Description
Drug addiction is a pervasive problem in society, as it produces major increases in health care costs, crime, and loss of productivity. With over 3 million long-term users in America alone, cocaine is one of the most identifiable and addictive drugs. Cocaine produces major neurological changes in the central nervous system, including widespread changes in gene expression. MicroRNAs are small, non-coding transcripts that regulate gene expression post-transcriptionally by preventing translation into function protein. Given that one miRNA can target several genes simultaneously, they have the potential to attenuate drug-induced changes in gene expression. We previously found that the microRNA miR-495 regulates several addiction-related genes (ARGs) and is highly expressed in the nucleus accumbens (NAc), an important brain region involved in reward and motivation. Furthermore, acute cocaine decreases miR-495 expression and increases ARG expression in the NAc. Therefore, the aim of this thesis was to determine the effect of miR-495 overexpression in the NAc on cocaine self-administration behavior. Male Sprague Dawley rats were trained to lever press for cocaine and were then infused with a lentivirus into the NAc that either overexpressed green fluorescent protein (GFP, control) or miR-495+GFP. We then tested the rats on several doses of cocaine on both a fixed ratio (5) and progressive ratio (PR) schedule of reinforcement. We performed a follow-up experiment that included the same viral manipulation and testing, but the reinforcer was switched to food pellets. We found that NAc miR-495 overexpression reduces cocaine self-administration on a PR, but not an FR5, schedule of reinforcement. We found no effects of miR-495 overexpression on food reinforcement. These data suggest that NAc miR-495 regulates genes involved in motivation for cocaine, but not general motivation based on the data with food reinforcement. Future studies will seek to determine the specific target genes responsible for our behavioral effects.
Date Created
2016-05
Contributors
- Galles, Nick (Author)
- Neisewander, Janet (Thesis director)
- Bastle, Ryan (Committee member)
- Foster, M. (Committee member)
- Barrett, The Honors College (Contributor)
Topical Subject
Resource Type
Extent
34 pages
Copyright Statement
In Copyright
Primary Member of
Series
Academic Year 2015-2016
Handle
https://hdl.handle.net/2286/R.I.36934
Level of coding
minimal
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System Created
- 2017-10-30 02:50:57
System Modified
- 2021-07-30 03:54:25
- 2 years 9 months ago
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