The overall aim of these studies is to determine whether impaired serotonin function confers vulnerability to the aggression increasing effects of alcohol among women. More specifically, we propose to study the effects of alcohol and plasma L-tryptophan manipulations (and ultimately serotonin levels in the central nervous system) on aggressive responding in female subjects under controlled laboratory conditions. A naturalistic laboratory procedure will be used, which provides the participating subject with the opportunity to aggress toward a fictitious person who ostensibly presents an aversive stimulus to the subject. To identify the complete time-course effects of alcohol and/or the plasma L-tryptophan manipulations on behavior, subjects' responses will be evaluated at periodic intervals before and following drink administration. The effects of alcohol and amino-acid drink mixtures, which either increase (T+) or decrease (T-) plasma L- tryptophan levels, will be compared. Of particular importance will be the effects of these drink manipulations in two groups of women, who differ in the severity of menstrual related symptoms, at two different phases of the menstrual cycle. This is important because serotonin function appears to vary across the menstrual cycle phase (lower function during premenstrual phase) and is affected by the degree of premenstrual symptomatology experienced (lower function in women with high levels of symptomatology). These factors should differentially affect the efficacy of the drink administration (alcohol and/or amino-acid drinks).
The specific aims of these laboratory studies are: l. To determine the differences in the effects of alcohol on aggression during the follicular and late- luteal (i.e., premenstrual) phases of the menstrual cycle; 2. To determine differences in the effects of the T+ and T- drinks on aggression during the follicular and late-luteal phases of the menstrual cycle; 3. To determine the interaction between alcohol combined with either the T+ or T- drinks on aggression; 4. To systematically examine how individuals with and without premenstrual symptomatology are differentially affected by the alcohol and L-tryptophan manipulation procedures; and 5. To determine how clinical instruments of aggression and impulsiveness are related to aggressive responding observed in the laboratory. These proposed studies will answer several questions regarding how alcohol, serotonin, premenstrual symptomatology, and the menstrual cycle are related to the susceptibility for aggressive behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012046-05
Application #
6629631
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Egli, Mark
Project Start
1999-09-01
Project End
2004-08-31
Budget Start
2003-06-01
Budget End
2004-08-31
Support Year
5
Fiscal Year
2003
Total Cost
$17,438
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Badawy, Abdulla A-B; Lake, Sarah L; Dougherty, Donald M (2014) Mechanisms of the pellagragenic effect of leucine: stimulation of hepatic tryptophan oxidation by administration of branched-chain amino acids to healthy human volunteers and the role of plasma free tryptophan and total kynurenines. Int J Tryptophan Res 7:23-32
Acheson, Ashley; Richard, Dawn M; Mathias, Charles W et al. (2011) Adults with a family history of alcohol related problems are more impulsive on measures of response initiation and response inhibition. Drug Alcohol Depend 117:198-203
Badawy, Abdulla A-B; Dougherty, Donald M; Richard, Dawn M (2010) Specificity of the acute tryptophan and tyrosine plus phenylalanine depletion and loading tests I. Review of biochemical aspects and poor specificity of current amino Acid formulations. Int J Tryptophan Res 2010:23-34
Badawy, Abdulla A-B; Dougherty, Donald M; Richard, Dawn M (2010) Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests Part II: Normalisation of the Tryptophan and the Tyrosine Plus Phenylalanine to Competing Amino Acid Ratios in a New Control Formulation. Int J Tryptophan Res 3:35-47
Richard, Dawn M; Dawes, Michael A; Mathias, Charles W et al. (2009) L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res 2:45-60
Badawy, Abdulla A-B; Doughrty, Donald M; Marsh-Richard, Dawn M et al. (2009) Activation of liver tryptophan pyrrolase mediates the decrease in tryptophan availability to the brain after acute alcohol consumption by normal subjects. Alcohol Alcohol 44:267-71
Dougherty, Donald M; Mathias, Charles W; Marsh-Richard, Dawn M et al. (2009) Distinctions in Behavioral Impulsivity: Implications for Substance Abuse Research. Addict Disord Their Treat 8:61-73
Dougherty, Donald M; Marsh-Richard, Dawn M; Mathias, Charles W et al. (2008) Comparison of 50- and 100-g L -tryptophan depletion and loading formulations for altering 5-HT synthesis: pharmacokinetics, side effects, and mood states. Psychopharmacology (Berl) 198:431-45
Dougherty, Donald M; Marsh-Richard, Dawn M; Hatzis, Erin S et al. (2008) A test of alcohol dose effects on multiple behavioral measures of impulsivity. Drug Alcohol Depend 96:111-20
Swann, Alan C; Moeller, F Gerard; Steinberg, Joel L et al. (2007) Manic symptoms and impulsivity during bipolar depressive episodes. Bipolar Disord 9:206-12

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