Author ORCID Identifier

https://orcid.org/0000-0001-6484-1608

Date Available

6-30-2021

Year of Publication

2021

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Arts and Sciences

Department/School/Program

Psychology

First Advisor

Dr. Chana K. Akins

Abstract

Ethanol is one of the most widely used and abused drugs. Problem use is associated with many different health problems and the economic burden is in the billions of dollars. Additionally, many people have difficulty controlling their ethanol consumption and about 5% of adults end up with an alcohol use disorder (AUD). Many people with an AUD often find themselves in a cycle of binge, remission, and relapse.

Following ethanol consumption ethanol enters the bloodstream from the small intestine where it gets distributed to peripheral tissues. Ethanol in the bloodstream is cleared from the system by the liver. The primary metabolism of ethanol uses alcohol dehydrogenase (ADH). Previous research indicates a significant sex difference in ADH activity in males and females depending on the tissue sample examined. Females tend to have higher ADH activity in liver samples than males. The purpose of the current study was to analyze sex differences in ADH levels following 12 days of ethanol administration (i.e., water or 2 g/kg) in male and female quail. Following the last daily treatment of ethanol, quail were euthanized and their livers were extracted and ADH was analyzed in liver homogenate samples. Females had higher ADH levels, heavier livers, and a greater liver to body weight ratio than males. In a second experiment, we aimed to develop a blood ethanol concentration (BEC) profile for both male and female quail. Quail were administered 0.75 or 2 g/kg and blood was collected at 0.5, 1, 2, 4, 6, 8, 12, 24 hours after gavage. Blood ethanol concentration was analyzed using an Analox. We found that quail had a fairly rapid increase in BECs followed by a steady and slow disappearance of ethanol from the blood samples. Female quail had a lower peak and a smaller area under the curve (AUC) than male quail. Female quail have higher ADH levels, which may be responsible for the metabolism of ethanol and therefore it follows that female quail would have less overall exposure to ethanol than male quail.

The conditioned place preference (CPP) paradigm uses a Pavlovian conditioning procedure to assess the reward or aversion of a conditioned stimulus. This method is often used to test the abuse potential of drugs in rodents. However, many of the cues associated with AUD tend to be visual in people, therefore, a visual species such as Japanese quail may be a better model to examine visual cues associated with AUD. Additionally, rodents often find an oral gavage to be aversive, whereas it is a typical administration for birds. The aim of the current study was to examine the rewarding properties of ethanol in Japanese quail using the CPP paradigm. Male and female quail received an ethanol (0, 0.75, or 2.0 g/kg) gavage and confined to their initially least preferred side based on a pretest (i.e. biased design) of the three-chamber CPP apparatus for 30 min on every other conditioning day. On alternate days, quail received a gavage of water and confined to the opposite side for 30 min. Quail received a total of 4 ethanol and 4 water conditioning trials on alternating days and locomotor activity was collected during conditioning trials. Twenty-four hours after the last conditioning trial, quail were allowed to freely roam the entire apparatus for 15 min. A difference score was calculated between time spent in the drug paired chamber (i.e. posttest) and time initially spent in the least preferred side (i.e. pretest). An ANOVA analysis revealed a significant effect of treatment. Post hocs revealed quail that received the 0.75 g/kg developed a CPP compared to the other groups, whereas quail treated with 2 g/kg developed an aversion to their drug paired side. Additionally, during conditioning days there was a significant interaction between time and treatment on locomotion. Specifically, animals that were treated with the 2 g/kg dose of ethanol had significantly less movement over the 30 min conditioning trials. Our results indicate that quail may be a good model to study AUD because they acquire both a CPA and CPP to an oral gavage of ethanol suggesting both the rewarding and aversive properties of ethanol are observable in this model.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2021.253

Funding Information

This study was supported by the National Institute on Alcohol Abuse and Alcoholism training grant T32 AA027488 awarded to Shannon E Eaton in 2019.

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