GSBS Dissertations and Theses

ORCID ID

0000-0001-8688-0704

Approval Date

12-8-2016

Document Type

Doctoral Dissertation

Academic Program

Neuroscience

Department

Psychiatry

First Thesis Advisor

Andrew R. Tapper

Keywords

Alcohol, dopamine, mice, nicotinic acetylcholine receptor, reward, behavior, sex difference, VTA, CPP, DID c-Fos

Abstract

Alcohol, recently named the most dangerous drug in the world, contributes to nearly 40% of violent crimes and fatal traffic accidents, increases risk of roughly 60 different diseases and injuries, and is responsible for 2.5 million deaths each year worldwide. Despite these staggering figures, treatments remain ineffective and riddled with adverse side effects, making successful use of even the most effective treatments unlikely. Moreover, many of the treatments, and the supporting research, have focused only on male subjects, despite sex differences in various alcohol-related behaviors.

Human alcohol use is frequently accompanied by nicotine use, and vice versa, suggesting a common mechanism of the two drugs. In fact, alcohol may act through the same family of receptors as nicotine, the nicotinic acetylcholine receptors (nAChRs), eliciting similar activation of the reward pathway as nicotine and other drugs of abuse. Studies have shown that nAChRs containing the α4 and/or α6 subunits are involved in nicotine-induced activation of the reward pathway, leading to the hypothesis that these same receptor subtypes may be important for alcohol effects in the brain as well.

Using male and female genetic mouse models and various behavioral assays, we have shown not only that these α4 and/or α6-containing nAChRs are involved in alcohol- related behaviors and activation of the reward pathway, but also show sex differences in this involvement. Uncovering the mechanism of alcohol in the brain, in males as well as in females, is an important step in developing targeted treatments for alcohol abuse.

DOI

10.13028/M2C88B

Rights and Permissions

Copyright is held by the author, with all rights reserved.

Available for download on Saturday, March 10, 2018

Share

COinS