Alcohol Abuse New Approaches to Treatment：治疗酒精滥用的新方法.pptVIP

Craving Alcohol: Genetic and Pharmacological Factors Kent Hutchison, Ph.D. University of Colorado - Boulder Objectives Background and Long-Term Objective Current treatments that target addiction are only modestly effective Develop more effective treatments Immediate Objectives Characterize the behavioral and biological mechanisms associated with the etiology of addiction Characterize genetic factors that influence these mechanisms Characterizing Pharmacological and Genetic Mechanisms Identify important behavioral phenotypes Identify and test underlying biological mechanisms Identify and test candidate genetic factors that may explain individual differences in these mechanisms and the behavioral phenotype Informs a pharmacogenetic approach to the development and testing of new treatments for addictive disorders Homer Simpson: An iIlustration of Phenotypic Heterogeneity Homer Simpson: An iIlustration of Phenotypic Heterogeneity Phenotypes of Interest Cue elicited craving for alcohol Pharmacological Mechanisms Genetic Factors Treatment development Subjective sensitivity to alcohol Stimulatory and Euphoric Effects Sedative Effects Physiological sensitivity to alcohol Startle Response Heart Rate Cue-Elicited Craving as a Phenotype Cue-Elicited Craving Clinically relevant Associated with loss of control and relapse Target of numerous biological and behavioral interventions Can be studied in the laboratory Triggered by environmental cues Triggered by small doses of alcohol Alcoholics report powerful craving and loss of control after initial drink Associated with a biological mechanism dopamine neurotransmission in midbrain, prefrontal areas, D2 and D4 receptors A personal description… Study 1: Testing the Biological Mechanism Would expect olanzapine (D2/D4 antagonist) to attenuate craving after a priming dose of alcohol Methods Sample - 26 heavy drinkers (Avg age= 23; Drinking days = 16; Drinks/Day = 5.8) Random assignment – Olanz (13), Pla (13) Two expe