Olanzapine reduces craving for alcohol: a DRD4 VNTR polymorphism by pharmacotherapy interaction.
Separate investigations have suggested that olanzapine, a D4 antagonist, decreases craving after a priming dose of alcohol and that the DRD4 variable number of tandem repeats (VNTR) polymorphism influences the expression of craving after a priming dose of alcohol. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving based on individual differences in DRD4 VNTR in a sample of heavy social drinkers. Participants were randomly assigned to receive olanzapine (5 mg) or a control medication (cyproheptadine, 4 mg) prior to consuming three alcoholic drinks. Participants completed subjective measures of craving and euphoria after each drink. Participants who were homozygous or heterozygous for the 7 (or longer) repeat allele of the DRD4 VNTR were classified as DRD4 L, while the other participants were classified as DRD4 S. The findings indicated that olanzapine reduces craving for alcohol at baseline for both DRD4 S and DRD4 L individuals, but only reduces craving after exposure to alcohol cues and after a priming dose of alcohol for DRD4 L individuals.
Hutchison
Kent E
KE
Department of Psychology, University of Colorado at Boulder, Boulder, CO 80309-0345, USA. KentH@psych.colorado.edu
Wooden
Angela
A
Swift
Robert M
RM
Smolen
Andrew
A
McGeary
John
J
Adler
Lawrence
L
Paris
Lyndee
L
D000328:Adult; D000339:Affect / Q000187:drug effects; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D016739:Behavior, Addictive / Q000188:drug therapy / Q000235:genetics; D001569:Benzodiazepines; D016022:Case-Control Studies; D002492:Central Nervous System Depressants; D016009:Chi-Square Distribution; D003463:Cues; D003533:Cyproheptadine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D007206:Individuality; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics*; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D012702:Serotonin Antagonists / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D001569:Benzodiazepines; D002492:Central Nervous System Depressants; D003533:Cyproheptadine; D000431:Ethanol; D000077152:Olanzapine; D010890:Pirenzepine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C493599:DRD4 protein, human