Dataset Information

Striatal dopamine in anhedonia: A simultaneous [¹¹C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

ABSTRACT:

Background

Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample.

Methods

Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [¹¹C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors.

Results

Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC.

Conclusions

Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.

SUBMITTER: Phillips RD

PROVIDER: S-EPMC10594643 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Striatal dopamine in anhedonia: A simultaneous [<sup>11</sup>C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

Phillips Rachel D RD Walsh Erin C EC Zürcher Nicole R NR Lalush David S DS Kinard Jessica L JL Tseng Chieh-En CE Cernasov Paul M PM Kan Delia D Cummings Kaitlin K Kelley Lisalynn L Campbell David D Dillon Daniel G DG Pizzagalli Diego A DA Izquierdo-Garcia David D Hooker Jacob M JM Smoski Moria J MJ Dichter Gabriel S GS

Psychiatry research. Neuroimaging 20230601

<h4>Background</h4>Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample.<h4>Methods</h4>Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task duri ...[more]

PMID: 37301129

Similar Datasets

Project description: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.

Project description:BackgroundCue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine (DA) transmission. Using [(11) C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST DA release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST blood oxygenation level-dependent (BOLD) responses to beer flavor are related to VST DA release and motivation to drink.MethodsMale beer drinkers (n = 28, age = 24 ± 2, drinks/wk = 16 ± 10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade(®) (appetitive control). We tested for correlations between BOLD activation in fMRI and VST DA responses in PET, and drinking-related variables.ResultsCompared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest.ConclusionsBoth imaging modalities showed a right-lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males) and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting.

Dataset Information

Striatal dopamine in anhedonia: A simultaneous [¹¹C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

Background

Methods

Results

Conclusions

Publications

Striatal dopamine in anhedonia: A simultaneous [<sup>11</sup>C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Striatal dopamine in anhedonia: A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

Background

Methods

Results

Conclusions

Publications

Striatal dopamine in anhedonia: A simultaneous [<sup>11</sup>C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Striatal dopamine in anhedonia: A simultaneous [¹¹C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.