Brain tyrosine level controls striatal dopamine synthesis in haloperidol-treated rats

1977 ◽  
Vol 41 (1) ◽  
pp. 1-6 ◽  
Author(s):  
M. C. Scally ◽  
I. Ulus ◽  
R. J. Wurtman
Keyword(s):  
Striatal Dopamine ◽  
Dopamine Synthesis

scholarly journals Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes

2021 ◽  
Author(s):  
Gemma Modinos ◽  
Anja Richter ◽  
Alice Egerton ◽  
Ilaria Bonoldi ◽  
Matilda Azis ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Outcomes ◽  
Mental States ◽  
Adverse Outcomes ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Hippocampal Activity ◽  
The Relationship

AbstractPreclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

scholarly journals Striatal dopamine synthesis capacity reflects smartphone social activity

iScience ◽  
2021 ◽  
pp. 102497
Author(s):  
Andrew Westbrook ◽  
Arko Ghosh ◽  
Ruben van den Bosch ◽  
Jessica I. Määttä ◽  
Lieke Hofmans ◽  
...  
Keyword(s):  
Social Activity ◽  
Striatal Dopamine ◽  
Dopamine Synthesis

scholarly journals O5.1. STRIATAL DOPAMINE AND REDUCED REWARD PREDICTION ERROR SIGNALING IN UNMEDICATED SCHIZOPHRENIA PATIENTS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Teresa Katthagen ◽  
Jakob Kaminski ◽  
Andreas Heinz ◽  
Ralph Buchert ◽  
Florian Schlagenhauf
Keyword(s):  
Prediction Error ◽  
Negative Symptoms ◽  
Ventral Striatum ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Positive Symptoms ◽  
Healthy Controls ◽  
Reward Prediction Error ◽  
Reward Prediction ◽  
Significant Difference

Abstract Background Increased striatal dopamine synthesis capacity (DSC) has consistently been reported in patients with schizophrenia (Sz). However, the functional mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error (RPE) signaling during reinforcement learning. Methods In this study, we investigated striatal DSC and RPEs and their association in unmedicated Sz and healthy controls. 23 healthy controls (HC) and 20 unmedicated Sz took part in an FDOPA-PET scan measuring DSC and underwent fMRI scanning, where they performed a reversal learning paradigm. We compared groups regarding DSC und neural RPE signals and probed the respective correlation (23 HC and 16 Sz for both measures). Results There was no significant difference between HC and Sz in DSC. Taking into account comorbid alcohol abuse revealed that only patients without such abuse showed elevated DSC in the associative and sensorimotor striatum, while those with abuse did not differ from HC. Patients performed worse during learning, accompanied by a reduced RPE signal in the ventral striatum. In HC, the DSC in the limbic striatum correlated with higher RPE signaling, while there was no significant association in patients. DSC in the associative striatum correlated with higher positive symptoms, and blunted RPE signaling was associated with negative symptoms. Discussion Our results suggest that dopamine modulation of RPE is impaired in schizophrenia. Furthermore, we observed a dissociation with elevated DSC in the associative and sensorimotor striatum contributing to positive symptoms and blunted RPE in the ventral striatum to negative symptoms.

scholarly journals S145. CORTICO-THALAMIC DYSCONNECTIVITY LINKS WITH ABERRANT STRIATAL DOPAMINE IN SCHIZOPHRENIA A SIMULTANEOUS 18F-DOPA-PET/RESTING-STATE FMRI STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S91-S91
Author(s):  
Mihai Avram ◽  
Felix Brandl ◽  
Franziska Knolle ◽  
Jorge Cabello ◽  
Claudia Leucht ◽  
...  
Keyword(s):  
Resting State ◽  
Dorsal Striatum ◽  
Correlation Coefficients ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Salience Network ◽  
Thalamic Nuclei ◽  
Cortical Networks ◽  
Sensorimotor Network ◽  
System Changes

Abstract Background In schizophrenia, among the most consistent brain changes are both aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei; however, it is unknown whether these changes are pathophysiologically related. Such a relationship is expected because cortico-thalamic-connectivity is modulated by striatal dopamine within topographically distinct, parallel but interacting cortico-basal-ganglia-thalamic circuits. We hypothesized: (1) Within-circuits, aberrant striatal dopamine contributes to aberrant cortico-thalamic-iFC, specifically, associative-striatum dopamine contributes to salience-network-thalamic-iFC, and sensorimotor-striatum dopamine to auditory-sensorimotor-network-thalamic-iFC. (2) Due to between-circuits interactions following an anterior-to-posterior gradient, salience-network-centered-system changes contribute to auditory-sensorimotor-network-centered-system changes. Methods To test these hypotheses, 19 patients with schizophrenia during symptomatic remission of positive symptoms and 19 age- and sex-comparable controls underwent simultaneous fluorodihydroxyphenyl-L-alanine positron emission tomography (18F-DOPA-PET) and resting-state functional magnetic resonance imaging (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure dopamine synthesis capacity (DSC), indicating striatal dopamine function; correlation coefficients between rs-fMRI time-series of cortical networks and thalamic regions-of-interest were used to measure iFC. Results In the salience-network(SAL)-centered-system, patients had reduced associative-striatum-DSC, which correlated positively with SAL-mediodorsal-thalamus-iFC and mediated the reduction of SAL-thalamic-iFC in patients. In the auditory-sensorimotor-network(ASM)-centered-system, patients had reduced sensorimotor-striatum-DSC, which correlated positively with ASM-ventrolateral-thalamus-iFC, but did not mediate increased ASM-thalamic-iFC in patients. Finally, aberrant DSC and iFC of the SAL-centered-system mediated corresponding changes in the ASM-centered-system. Discussion Results demonstrate that cortico-thalamic-dysconnectivity links with aberrant striatal dopamine in schizophrenia - in a topographically distinct way, with an anterior-to-posterior gradient, and primary changes in the SAL-centered system.

scholarly journals Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work

Science ◽  
2020 ◽  
Vol 367 (6484) ◽  
pp. 1362-1366 ◽  
Author(s):  
A. Westbrook ◽  
R. van den Bosch ◽  
J. I. Määttä ◽  
L. Hofmans ◽  
D. Papadopetraki ◽  
...  
Keyword(s):  
Sequential Sampling ◽  
D2 Receptor ◽  
Cognitive Effort ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Cost Ratio ◽  
Cost Information ◽  
Cognitive Work ◽  
Sequential Sampling Model ◽  
Dopamine Signaling

Stimulants such as methylphenidate are increasingly used for cognitive enhancement but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, whereas methylphenidate and sulpiride, a selective D2 receptor antagonist, increased cognitive motivation more for participants with lower synthesis capacity. A sequential sampling model informed by momentary gaze revealed that decisions to expend effort are related to amplification of benefit-versus-cost information attended early in the decision process, whereas the effect of benefits is strengthened with higher synthesis capacity and by methylphenidate. These findings demonstrate that methylphenidate boosts the perceived benefits versus costs of cognitive effort by modulating striatal dopamine signaling.

Inhibition of striatal dopamine synthesis in rats injected chronically with neuroleptics in their early life

1975 ◽  
Vol 288 (1) ◽  
pp. 97-102 ◽  
Author(s):  
L. Velley ◽  
G. Blanc ◽  
J. P. Tassin ◽  
A. M. Thierry ◽  
J. Glowinski
Keyword(s):  
Early Life ◽  
Striatal Dopamine ◽  
Dopamine Synthesis

scholarly journals Increased Striatal Dopamine Synthesis Capacity in Gambling Addiction

2018 ◽  
Vol 83 (12) ◽  
pp. 1036-1043 ◽  
Author(s):  
Ruth J. van Holst ◽  
Guillaume Sescousse ◽  
Lieneke K. Janssen ◽  
Marcel Janssen ◽  
Anne S. Berry ◽  
...  
Keyword(s):  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Gambling Addiction

scholarly journals The cognitive effects of a promised bonus do not depend on dopamine synthesis capacity

2020 ◽  
Author(s):  
Lieke Hofmans ◽  
Ruben van den Bosch ◽  
Jessica I. Määttä ◽  
Robbert-Jan Verkes ◽  
Esther Aarts ◽  
...  
Keyword(s):  
Cognitive Control ◽  
Incentive Motivation ◽  
Striatal Dopamine ◽  
Differential Sensitivity ◽  
Dopamine Synthesis ◽  
Negative Effects ◽  
Societal Relevance ◽  
Stroop Paradigm ◽  
Reward Motivation ◽  
Reward Effects

ABSTRACTReward motivation is known to enhance cognitive control. However, detrimental effects have also been observed, which have been attributed to overdosing of already high baseline dopamine levels by further dopamine increases elicited by reward cues. Aarts et al. (2014) indeed demonstrated, in 14 individuals, that reward effects depended on striatal dopamine synthesis capacity, measured with [18F]FMT-PET: promised reward improved Stroop control in low-dopamine individuals, while impairing it in high-dopamine individuals. Here, we aimed to assess this same effect in 44 new participants, who had previously undergone an [18F]DOPA-PET scan to quantify dopamine synthesis capacity. This sample performed the exact same rewarded Stroop paradigm as in the prior study. However, we did not find any correlation between reward effects on cognitive control and striatal dopamine synthesis capacity. The discrepancy between the current and our previous findings might reflect the use of different radiotracers for indexing dopamine synthesis capacity.STATEMENT OF RELEVANCEReward motivation is generally thought to enhance cognitive control, but paradoxical negative effects of rewards on cognitive control have also been observed. A previous PET study demonstrated that reward effects on Stroop control depended on baseline striatal dopamine synthesis capacity, indexed by uptake of the radiotracer [18F]FMT. The sample size is this study was very small for a between-subject correlational design. Replicating the exact same Stroop paradigm within a larger sample is therefore crucial to robustly establish the mechanistic link between incentive motivation and cognitive control and advancing our understanding of who chokes under pressure and why, a topic of great societal relevance today. The present study did not reveal any correlation between reward effects on cognitive control and striatal dopamine synthesis capacity, indexed with [18F]FDOPA-PET. Future studies might consider putative differential sensitivity of the radiotracer [18F]FMT and [18F]FDOPA, while also addressing other indices of dopamine transmission.

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