Effect of miRNA-138 Injected into the Medial Habenula on Nicotine Intake and Preference

Undergraduate Honors Thesis

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/fx719m98t

Abstract

Nicotine is one of the most commonly abused drugs in the world today and is associated with many adverse health outcomes, including death. Nicotine binds to nicotinic acetylcholine receptors (nAChRs) in the brain reward pathway, triggering the release of a number of neurotransmitters, including dopamine. The goal of the current study was to determine whether miR-138, a miRNA that targets and reduces β4 subunit gene expression, injected into the medial habenula would lead to changes in nicotine intake/preference. We hypothesized that miR-138 would down regulate β4 expression, leading to decreased aversion to nicotine and increased nicotine intake/preference. Male and female C57BL/6 mice were unilaterally injected with an adeno-associated virus containing either miR-138 or a scrambled control miRNA sequence. Mice were then given access to water and increasing concentrations of a nicotine solution. We measured overall fluid consumption as well as nicotine intake. Mice injected with the miR-138 showed a trend for reduced nicotine intake and consumption compared to controls. Preliminary results were not statistically significant, but suggest that miR-138 injected into the medial habenula does not affect nicotine intake/preference. The current results suggest that reducing the expression of β4 subunits in the medial habenula via miR-138 leads to reductions in nicotine reward-related behavior, which does not support our initial hypothesis.

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