Undergraduate Honors Theses

Thesis Defended

Spring 2017

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Integrative Physiology

First Advisor

Dr. Marissa Ehringer

Second Advisor

Dr. David Sherwood

Third Advisor

Dr. Susan Hendrickson

Abstract

Nicotine addiction is the most common form of addiction in the United States. Nicotinic acetylcholine receptors (nAChRs) are the major binding site for nicotine, which are ligand-gated ion channels consisting of combinations of five alpha and/or beta subunits that form the receptor pore. Previous research suggests that expression of the β4 nAChR subunit is involved in nicotine aversion. Further, the β4 subunit is expressed at relatively high levels in the medial habenula, and the expression of the gene coding for β4 can be decreased by miR-138, a small non-coding microRNA (miRNA) that naturally regulates gene expression. Mice were injected with a GFP-labeled adeno-associated virus containing either miR-138 or a scrambled-miRNA control. Next using a two-bottle choice protocol, nicotine and tastant drinking were measured and brains were collected to assess injection site location. Among mice with confirmed injection in the medial habenula, consumption and preference of nicotine as well as quinine was significantly lower in miR-138 treated mice than scrambled controls. This research will provide a greater understanding of the biological mechanisms of β4 on nicotine addiction and gives rise to potential treatments for nicotine dependence.

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