Parallel role for the dopamine D1 receptor in gambling and amphetamine reinforcement in healthy volunteers.
This study investigated the role of dopamine, and specifically the D1 receptor (D1R), in the reinforcing effects of a slot-machine game in healthy volunteers ( n=30). To compare gambling and drug effects, subjects received the prototypic psychostimulant drug d-amphetamine (AMPH; 20 mg) in a multi-session, placebo-controlled design. To isolate D1R, half the subjects were pretreated with the preferential D2 receptor antagonist haloperidol (HAL; 3 mg), and the other half with the mixed D1-D2 antagonist fluphenazine (FLU; 3 mg) before the game (Phase I) and AMPH (Phase II). HAL decreased and FLU increased the post-game desire to gamble and post-AMPH desire to take AMPH again, as well as amphetamine scale ratings on the Addiction Research Center Inventory after gambling and AMPH. The effects of the antagonists on desire to gamble and to take AMPH again were significantly intercorrelated. HAL increased and FLU decreased the salience of negative affective words on a rapid reading task after both reinforcers. HAL also decreased the salience of gambling words after AMPH. Both reinforcers increased diastolic blood pressure equally under antagonists and placebo. Results indicate that D1R plays a parallel role in the psychostimulant-like, incentive-motivational, and salience-enhancing effects of gambling and AMPH. Moderate D1R activation appears to optimize these effects in healthy subjects.
Centre for Addiction and Mental Health, Toronto, Canada.
Martin H
MH
Zack
Centre for Addiction and Mental Health, Toronto, Canada.
Daniela S
DS
Lobo
Centre for Addiction and Mental Health, Toronto, Canada.
Candice
C
Biback
Centre for Addiction and Mental Health, Toronto, Canada.
Tim
T
Fang
Centre for Addiction and Mental Health, Toronto, Canada.
Kelly
K
Smart
Centre for Addiction and Mental Health, Toronto, Canada.
Daniel
D
Tatone
Centre for Addiction and Mental Health, Toronto, Canada.
Aditi
A
Kalia
Centre for Addiction and Mental Health, Toronto, Canada.
Daniel
D
Digiacomo
Centre for Addiction and Mental Health, Toronto, Canada.
James L
JL
Kennedy
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D016739:Behavior, Addictive / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D005715:Gambling / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D009042:Motivation / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012054:Reinforcement, Psychology
D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D000661:Amphetamine; D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine
D1; Gambling; amphetamine; reinforcement