Document Type

Dissertation

Date of Award

1976

Keywords

Alcohol, Physiological effect, Brain chemistry, Psychopharmacology

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology

First Advisor

Peter J. Donovick

Second Advisor

John L. Fuller

Third Advisor

Carole Hansult

Abstract

A review of the evidence linking gene action with the behavioral response of laboratory mamals to ethanol has been attempted. Studies examining the relationship between an animal's genotype and its preference for alcohol are dealt with first. Genetic factors were found to strongly affect the magnitude of alcohol consumption exhibited by both mice and rats. A second section reviews the work which has studied the influence of genetics on the behavioral response that follows an acute alcohol dose. A major role of genetics in determining the psychopharmacological response to alcohol is indicated.

The sections dealing with genetics and alcohol are followed by an examination of the interactions which have been demonstrated between alcohol and brain catecholamines. The evidence is considered under five areas of study; 1.) the effects of ethanol on brain catecholamine levels and turnover; 2.) ethanol's action on brain cyclic 3', 5'-adenosine monophosphate; 3.) the correlation between alcohol preference and brain catecholamine measures; 4.) the effects of drugs, which have adrenergic action, on the behavioral response to ethanol and; 5.) the theory and evidence for the formation of catecholamine—derived alkaloids from ethanol metabolites.

The fourth major section is an overview of the studies demonstrating genetic regulation of catecholamine synthesis, endogenous levels, and turnover rate. The final section of the review summarizes the evidence of the four previous parts and proposes a theory of the action of ethanol on the mammalian central nervous system.

Two original research studies follow the review and are entitled "Motor Responses Following Acute Alcohol Administration And Their Relation To Brain Catecholamines In Mice Selected For Diffeenrtial Alcohol-Induced Sleep—Time", and " Mice Selected For Differences In Ethanol—Induced Sleep—time Show Differences In Ethanol Consumption". Both studies employed two lines of mice selectively bred for 18 generations for differences in alcohol induced sleep-time. One line of mice, the LS line, responds with a characteristically long sleep—time following a hypnotic alcohol dose. The other mouse line, the SS line, shows a very short sleep—time following the same ethanol dose.

The first study found that LS animals showed higher sensitivity than SS mice to the motor incoordinating effects of low alcohol doses. With respect to activity, SS mice were more sensitive, compared to LS mice, to the motor stimulation seen following low doses of ethanol. Mice of the SS line also showed higher levels of baseline activity than LS animals. No significant differences in brain catecholamine levels were found between the lines.

The second study found that SS mice consume more sweetened ethanol solution than LS mice. Female mice consumed more of the sweet ethanol than did males. The influence of genotype was compared with the effect of 30 days of ethanol intake. It was noted that genotype was the predominant factor in determining the amount of ethanol consumed in a choice between sweetened alcohol and an equally sweet non-alcoholic alternative.

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