Abstract
Rationale
Animal research suggests that anticipation of reward can elicit dopamine release in the nucleus accumbens (NAcc). Human functional magnetic resonance imaging (FMRI) research further suggests that reward anticipation can increase local blood oxygen level dependent (BOLD) signal in the NAcc. However, the physiological relationship between dopamine release and BOLD signal increases in the NAcc has not yet been established.
Objectives
This review considers pharmacological MRI (phMRI) evidence for a directional relationship between NAcc dopamine release and BOLD signal, as well as implications for human psychopathological symptoms.
Results
Accumulating phMRI evidence supports a simple model in which NAcc dopamine release activates postsynaptic D1 receptors, which changes postsynaptic membrane potential, eventually increasing local BOLD signal. This continuing influence can change on a second-to-second basis.
Conclusions
Dopamine release in the NAcc appears to increase local BOLD signal via agonism of postsynaptic D1 receptors. Such a physiological mechanism implies that FMRI may be used to track symptoms related to NAcc dopaminergic dysregulation in psychiatric disorders including schizophrenia and attention deficit/hyperactivity disorder.
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Notes
Measuring NAcc activity. Because dopamine release fluctuates rapidly in the NAcc (see Fig. 1), both spatial and temporal resolutions present critical considerations for researchers. Presently available methods differ in spatial and temporal resolution (current estimates are listed below for each). However, future innovations may well increase the resolution of any of these methods. Because they are invasive, microdialysis and cyclic voltammetry are primarily used in rodents, whereas PET and FMRI are less invasive and so commonly used in humans. a Microdialysis (0.3 mm, 120 s): A probe containing concentric tubes is positioned in the brain region of interest. Synthetic extracellular fluid is passed from the outer tube to the inner tube. Extracellular molecules (e.g., dopamine) are also sucked into the inner tube, which can then be analyzed for chemical content with high performance liquid or gas chromatography. b Cyclic voltammetry (0.01 mm, 0.100 s): A probe containing two adjacent electrical wires is positioned in the brain region of interest. A variable current is passed from one wire to the other, and electron flow through intermediary material is measured. Certain molecules increase current flow at specific voltages. Given the absence of other similarly reactive molecules (e.g., norepinephrine), and controlling for background current, the presence of dopamine can be inferred. c Radioligand positron emission tomography (8 mm, 3,600 s): A compound containing radioactively tagged molecules that mimic dopamine is injected into the subject. The tagged molecules travel to the brain and attach to dopamine receptors. The tags decay, emitting two positrons in opposite directions, and a camera detects the emissions and computes their point of origin. As the tags decay, subjects receive an experimental treatment that releases dopamine (e.g., receive an amphetamine injection) or a control treatment that does not (e.g., receive a placebo injection). Once released, dopamine displaces tagged molecules from receptors, and a difference in positron emission in that specific locale between experimental and control conditions can later be computed. d Functional magnetic resonance imaging: (4 mm, 1 s): A large magnet aligns protons in subjects’ brains. A smaller coil then emits magnetic pulses that flip the protons’ orientation and subsequently assesses the speed and spin with which protons return to their original orientation. Subjects engage in a task that elicits more or less synaptic activity. In brain regions with increased synaptic activity, oxygen consumption increases, followed by a disproportionate increase in local venous oxygen with an approximate lag of 4–6 s. “Ballooning” of these veins with oxygenated blood creates a small venous pocket of demagnetization, which has been called “blood oxygen level dependent” (BOLD) signal. Changes in regional BOLD signal can be compared across experimental versus control task conditions. Whereas microdialysis and radioligand PET have greater chemical specificity for detecting dopamine, cyclic voltammetry and FMRI have greater temporal resolution for detecting rapid changes in NAcc activity. As each method has different strengths, each can make unique contributions to researchers’ understanding of changes in NAcc dopamine.
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Acknowledgment
We thank G. Elliott Wimmer, Peter Shizgal, and three anonymous reviewers for helpful comments on prior drafts of the manuscript. During manuscript preparation, BK was supported by NIDA grant DA020615-01.
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Knutson, B., Gibbs, S.E.B. Linking nucleus accumbens dopamine and blood oxygenation. Psychopharmacology 191, 813–822 (2007). https://doi.org/10.1007/s00213-006-0686-7
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DOI: https://doi.org/10.1007/s00213-006-0686-7