Ethanol craving in patients is a significant clinical problems with a poorly understood underlying neurobiology. This application represents the resubmission of the competitive renewal of a research program illum inating the clinical neurobiology of this important problem. We outline a new study, building on the initial year of progress, that will further evaluate the contributions of noradrenergic systems to ethanol craving. This is part of a ling- term attempt to elucidate a model describing the unique and interactive contributions of noradrenergic and serotonergic systems to the neurobiology of ethanol craving in alcoholics. Noradrenergic systems appear to modulate arousal-related reactivity, while serotonergic system a modulate the processing of ethanol-related cues and impulse control regarding ethanol self-administration. Background: The investigative team collaborating in this application has validated a laboratory-based paradigm designed to stimulate ethanol craving in alcoholic patients. During the initial year of the two-year previous R01, data were collected implicating noradrenergic systems in ethanol cue reactivity and suggesting that craving may be modulated by tryptophan depletion. Objectives: To determine whether transient inhibition of noradrenergic function, produced by the 2-adrenergic agonist, clonidine, reduces the magnitude of alcohol cue-induced craving in sober alcohol dependent patients. Methods: In an ongoing study, individuals meeting DSM-IV criteria for alcohol will be recruited, 1-3 moths post-detoxification. Patients will complete an initial alcohol cue exposure session. Patients exhibiting al least a 20% increase in craving in the initial cue exposure session will complete two additional cue-exposure tests. Cue exposure sessions will be preceded by placebo or clonidine. Each test day will be scheduled one week apart, and the sequence will be randomized. Preliminary Results: Preliminary results indicate that clonidine appeared to reduce cue-induced craving for alcohol. Implications: These data are part of a larger body of work that attempts to evaluate an heuristic model, described in this application, in which noradrenergic and serotonergic systems differentially contribute to the modulation of cue-induced craving.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010107-04
Application #
2748439
Study Section
Special Emphasis Panel (ZAA1-CC (M1))
Project Start
1995-01-01
Project End
2000-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Yale University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Petrakis, Ismene L; Buonopane, Alessandra; O'Malley, Stephanie et al. (2002) The effect of tryptophan depletion on alcohol self-administration in non-treatment-seeking alcoholic individuals. Alcohol Clin Exp Res 26:969-75
Petrakis, I L; Trevisan, L; Boutros, N N et al. (2001) Effect of tryptophan depletion on alcohol cue-induced craving in abstinent alcoholic patients. Alcohol Clin Exp Res 25:1151-5
Petrakis, I L; Trevisan, L; D'Souza, C et al. (1999) CSF monoamine metabolite and beta endorphin levels in recently detoxified alcoholics and healthy controls: prediction of alcohol cue-induced craving? Alcohol Clin Exp Res 23:1336-41