The overall objective of this project is to study stress-alcohol interactions in male and female rats. Several unique and important questions will be addressed: How does a stressful situation affect the biochemical homeostasis (plasma catecholamines) of the rat? What is the genetic component of this stress response? How does alcohol reduce and antagonize the stress response? Are rats which show a large stress response more affected by alcohol than are rats which show a low stress response? Do high or low stress responders differ in their voluntary alcohol intake during rest and stress? What other biochemical changes (brain biogenic amines, other plasma biochemicals) accompany the plasma catecholamine stress response? What are the correlations between biochemical and behavioral stress responses? Do male and female animals respond differently to stress and/or alcohol? The proposed experiments are a continuation of ongoing studies in the laboratory of the principal investigator designed to answer the above questions. They involve: 1) breeding of rats for their plasma catecholamine stress response by mating """"""""high"""""""" and """"""""low"""""""" stress responders selectively; 2) measurements of a number of plasma and brain biochemicals in these selectively bred animals over generations; 3) study of behavioral correlates in these selectively bred rats and 4) determination of voluntary alcohol consumption in these selectively bred """"""""high"""""""" and """"""""low"""""""" stress responders during rest and stress. Indirect evidence is available that stress and a genetic vulnerability play a role in the excessive alcohol consumption of some individuals. However, direct evidence on the role of stress and genetics in the etiology of alcoholism are often difficult to obtain in man. This study will supply scientific data on the stress- alcohol interaction and its genetic component. Our data can then be used to interpret more meaningful human studies, to identify individuals at high risk for alcoholism and to prevent or treat alcoholism by antagonizing specific stress responses with measures other than alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA006017-06
Application #
3109267
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1983-12-01
Project End
1990-12-31
Budget Start
1989-02-01
Budget End
1990-12-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Milakofsky, L; Harris, N; Vogel, W H (1996) Effect of repeated stress on a number of plasma amino acids and related compounds in young and old rats. Physiol Behav 60:969-71
Milakofsky, L; Harris, N; Vogel, W H (1993) Effects of repeated stress on plasma arginine levels in young and old rats. Physiol Behav 54:725-8
Milakofsky, L; Harris, N; Vogel, W H (1993) Effect of repeated stress on plasma catecholamines and taurine in young and old rats. Neurobiol Aging 14:359-66
Rammsayer, T H; Vogel, W H (1992) Pharmacologic properties of the internal clock underlying time perception in humans. Neuropsychobiology 26:71-80
Ferraro, T N; Carrozza, D P; Vogel, W H (1991) In vivo microdialysis study of brain ethanol concentrations in rats following oral self-administration. Alcohol Clin Exp Res 15:504-7
Netter, P; Vogel, W H (1990) The effect of drinking habit on catecholamine and behavioral responses to stress and ethanol. Neuropsychobiology 24:149-58
Ferraro, T N; Weyers, P; Carrozza, D P et al. (1990) Continuous monitoring of brain ethanol levels by intracerebral microdialysis. Alcohol 7:129-32
Vogel, W H; Netter, P (1990) The effect of ethanol on stress-induced tachycardia. Arch Psychol (Frankf) 142:9-23
Hofford, J M; Milakofsky, L; Vogel, W H et al. (1990) The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels. Am Rev Respir Dis 141:902-8
Taylor, J; Weyers, P; Harris, N et al. (1989) The plasma catecholamine stress response is characteristic for a given animal over a one-year period. Physiol Behav 46:853-6

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