title: Risky decision-making and ventral striatal dopamine responses to amphetamine: a positron emission tomography [(11)C]raclopride study in healthy adults.
abstract: Recent functional magnetic resonance imaging (fMRI) studies have provided compelling evidence that corticolimbic brain regions are integrally involved in human decision-making. Although much less is known about molecular mechanisms, there is growing evidence that the mesolimbic dopamine (DA) neurotransmitter system may be an important neural substrate. Thus far, direct examination of DA signaling in human risk-taking has centered on gambling disorder. Findings from several positron emission tomography (PET) studies suggest that dysfunctions in mesolimbic DA circuits may play an important role in gambling behavior. Nevertheless, interpretation of these findings is currently hampered by a need for better understanding of how individual differences in regional DA function influence normative decision-making in humans. To further our understanding of these processes, we used [(11)C]raclopride PET to examine associations between ventral striatal (VS) DA responses to amphetamine (AMPH) and risky decision-making in a sample of healthy young adults with no history of psychiatric disorder, Forty-five male and female subjects, ages 18-29 years, completed a computerized version of the Iowa Gambling Task. Participants then underwent two 90-minute PET studies with high specific activity [(11)C]raclopride. The first scan was preceded by intravenous saline; the second, by intravenous AMPH (0.3mg/kg). Findings of primary analyses showed that less advantageous decision-making was associated with greater right VS DA release; the relationship did not differ as a function of gender. No associations were observed between risk-taking and left VS DA release or baseline D2/D3 receptor availability in either hemisphere. Overall, the results support notions that variability in striatal DA function may mediate inter-individual differences in risky decision-making in healthy adults, further suggesting that hypersensitive DA circuits may represent a risk pathway in this population.
authors: Department of Family and Community Health, University of Maryland School of Nursing, Baltimore, MD 21201, USA; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: oswald@son.umaryland.edu.
authors: Lynn M
authors: LM
authors: Oswald
authors: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Gary S
authors: GS
authors: Wand
authors: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Dean F
authors: DF
authors: Wong
authors: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Clayton H
authors: CH
authors: Brown
authors: The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Hiroto
authors: H
authors: Kuwabara
authors: The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: James R
authors: JR
authors: Brašić
mesh_terms: D000293:Adolescent; D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003657:Decision Making / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D005715:Gambling / Q000000981:diagnostic imaging / Q000523:psychology; D006801:Humans; D007206:Individuality; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D012309:Risk-Taking; D012727:Sex Characteristics; D066328:Ventral Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine
keywords: Amphetamine; Decision-making; Dopamine; Human; Positron emission tomography (PET); Ventral striatum