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International Journal of Environmental... Sep 2022Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined...
Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined associations between the work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic nervous system activity, indicative of stress. We recruited participants (n = 219; 2018-2019) from a cardiovascular risk cohort to investigate workplace culture, well-being, and stress. Participants completed seven questionnaires. Urine samples were used to measure catecholamines and their metabolites by LC/MS/MS. Pearson correlation and linear regression models were used after adjusting for demographics and creatinine. Participants reporting higher well-being had lower urinary levels of dopamine, serotonin, and 3-methoxytyramine. Participants reporting a more engaged and more positive workplace had lower levels of dopamine and 3-methoxytyramine. Reported workplace isolation was correlated with higher levels of dopamine and 3-methoxytyramine. Given correlations between catecholamines, we used 3-methoxytyramine for linear regression. In fully adjusted models, in environments with a more positive culture, levels of 3-methoxytyramine remained lower (β = -0.065 ± 0.025, = 0.01) and indicated a positive association between workplace isolation and 3-methoxytyramine (β = 0.064 ± 0.030, = 0.04). These findings are consistent with an important relationship between workplace environment and sympathetic nervous system activity.
Topics: Biomarkers; Catecholamines; Creatinine; Dopamine; Humans; Serotonin; Tandem Mass Spectrometry; Workplace
PubMed: 36231223
DOI: 10.3390/ijerph191911920 -
Sleep Medicine Clinics Jun 2021For a long time, dopaminergic treatment (DT) was the medication for restless legs syndrome. Although DT is effective and safe over the short-term, complications develop... (Review)
Review
For a long time, dopaminergic treatment (DT) was the medication for restless legs syndrome. Although DT is effective and safe over the short-term, complications develop over longer periods, including augmentation, tolerance, and impulse control disorders. Nowadays, it is recommended that first-line treatment should be alpha-2 ligands, which are more effective in the absence of previous DT. As a second-line treatment, opioids, such as oxycodone extended-release with naloxone, are approved in Europe. Brain iron should be monitored before and during treatment and corrected if necessary. Two new promising non-DTs are being developed: perampanel and dipyridamole. More research is needed.
Topics: Analgesics, Opioid; Dopamine; Humans; Iron; Ligands; Randomized Controlled Trials as Topic; Restless Legs Syndrome; Treatment Outcome
PubMed: 33985652
DOI: 10.1016/j.jsmc.2021.02.003 -
PLoS Computational Biology Mar 2021Slow-timescale (tonic) changes in dopamine (DA) contribute to a wide variety of processes in reinforcement learning, interval timing, and other domains. Furthermore,...
Slow-timescale (tonic) changes in dopamine (DA) contribute to a wide variety of processes in reinforcement learning, interval timing, and other domains. Furthermore, changes in tonic DA exert distinct effects depending on when they occur (e.g., during learning vs. performance) and what task the subject is performing (e.g., operant vs. classical conditioning). Two influential theories of tonic DA-the average reward theory and the Bayesian theory in which DA controls precision-have each been successful at explaining a subset of empirical findings. But how the same DA signal performs two seemingly distinct functions without creating crosstalk is not well understood. Here we reconcile the two theories under the unifying framework of 'rational inattention,' which (1) conceptually links average reward and precision, (2) outlines how DA manipulations affect this relationship, and in so doing, (3) captures new empirical phenomena. In brief, rational inattention asserts that agents can increase their precision in a task (and thus improve their performance) by paying a cognitive cost. Crucially, whether this cost is worth paying depends on average reward availability, reported by DA. The monotonic relationship between average reward and precision means that the DA signal contains the information necessary to retrieve the precision. When this information is needed after the task is performed, as presumed by Bayesian inference, acute manipulations of DA will bias behavior in predictable ways. We show how this framework reconciles a remarkably large collection of experimental findings. In reinforcement learning, the rational inattention framework predicts that learning from positive and negative feedback should be enhanced in high and low DA states, respectively, and that DA should tip the exploration-exploitation balance toward exploitation. In interval timing, this framework predicts that DA should increase the speed of the internal clock and decrease the extent of interference by other temporal stimuli during temporal reproduction (the central tendency effect). Finally, rational inattention makes the new predictions that these effects should be critically dependent on the controllability of rewards, that post-reward delays in intertemporal choice tasks should be underestimated, and that average reward manipulations should affect the speed of the clock-thus capturing empirical findings that are unexplained by either theory alone. Our results suggest that a common computational repertoire may underlie the seemingly heterogeneous roles of DA.
Topics: Attention; Bayes Theorem; Cognition; Computational Biology; Dopamine; Humans; Models, Neurological; Reinforcement, Psychology
PubMed: 33760806
DOI: 10.1371/journal.pcbi.1008659 -
Proceedings of the National Academy of... Mar 2023Dopamine (DA) loss in Parkinson's disease (PD) causes debilitating motor deficits. However, dopamine is also widely linked to reward prediction and learning, and the...
Dopamine (DA) loss in Parkinson's disease (PD) causes debilitating motor deficits. However, dopamine is also widely linked to reward prediction and learning, and the contribution of dopamine-dependent learning to movements that are impaired in PD-which often do not lead to explicit rewards-is unclear. Here, we used two distinct motor tasks to dissociate dopamine's acute motoric effects vs. its long-lasting, learning-mediated effects. In dopamine-depleted mice, motor task performance gradually worsened with task exposure. Task experience was critical, as mice that remained in the home cage during the same period were relatively unimpaired when subsequently probed on the task. Repeated dopamine replacement treatments acutely rescued deficits and gradually induced long-term rescue that persisted despite treatment withdrawal. Surprisingly, both long-term rescue and parkinsonian performance decline were task specific, implicating dopamine-dependent learning. D1R activation potently induced acute rescue that gradually consolidated into long-term rescue. Conversely, reduced D2R activation potently induced parkinsonian decline. In dopamine-depleted mice, either D1R activation or D2R activation prevented parkinsonian decline, and both restored balanced activation of direct vs. indirect striatal pathways. These findings suggest that reinforcement and maintenance of movements-even movements not leading to explicit rewards-are fundamental functions of dopamine and provide potential mechanisms for the hitherto unexplained "long-duration response" by dopaminergic therapies in PD.
Topics: Mice; Animals; Dopamine; Neurons; Corpus Striatum; Learning; Parkinson Disease
PubMed: 36920928
DOI: 10.1073/pnas.2213093120 -
Integrative and Comparative Biology Jul 2021Goal-directed learning is a key contributor to evolutionary fitness in animals. The neural mechanisms that mediate learning often involve the neuromodulator dopamine. In... (Review)
Review
Goal-directed learning is a key contributor to evolutionary fitness in animals. The neural mechanisms that mediate learning often involve the neuromodulator dopamine. In higher order cortical regions, most of what is known about dopamine's role is derived from brain regions involved in motivation and decision-making, while significantly less is known about dopamine's potential role in motor and/or sensory brain regions to guide performance. Research on rodents and primates represents over 95% of publications in the field, while little beyond basic anatomy is known in other vertebrate groups. This significantly limits our general understanding of how dopamine signaling systems have evolved as organisms adapt to their environments. This review takes a pan-vertebrate view of the literature on the role of dopamine in motor/sensory cortical regions, highlighting, when available, research on non-mammalian vertebrates. We provide a broad perspective on dopamine function and emphasize that dopamine-induced plasticity mechanisms are widespread across all cortical systems and associated with motor and sensory adaptations. The available evidence illustrates that there is a strong anatomical basis-dopamine fibers and receptor distributions-to hypothesize that pallial dopamine effects are widespread among vertebrates. Continued research progress in non-mammalian species will be crucial to further our understanding of how the dopamine system evolved to shape the diverse array of brain structures and behaviors among the vertebrate lineage.
Topics: Animals; Dopamine; Learning; Motivation; Motor Cortex; Neuronal Plasticity; Vertebrates
PubMed: 33822047
DOI: 10.1093/icb/icab019 -
Neuropharmacology Sep 2020
Topics: Animals; Antipsychotic Agents; Brain; Dopamine; Humans
PubMed: 32533978
DOI: 10.1016/j.neuropharm.2020.108181 -
Advances in Colloid and Interface... Sep 2021Dopamine-based materials have attracted widespread interest due to the outstanding physicochemical and biological properties. Since the first report on polydopamine... (Review)
Review
Dopamine-based materials have attracted widespread interest due to the outstanding physicochemical and biological properties. Since the first report on polydopamine (PDA) films, great efforts have been devoted to develop new fabrication strategies for obtaining novel nanostructures and desirable properties. Among them, one-pot co-assembly strategy offers a unique pathway for integrating multiple properties and functions into dopamine-based platform in a single simultaneous co-deposition step. This review focuses on the state of the art development of one-pot multicomponent self-assembly of dopamine-based materials and summarizes various single-step co-deposition approaches, including PDA-assisted adaptive encapsulation, co-assembly of dopamine with other molecules through non-covalent interactions or covalent interactions. Moreover, emerging applications of dopamine-based materials in the fields ranging from sensing, cancer therapy, catalysis, oil/water separation to antifouling are outlined. In addition, some critical remaining challenges and opportunities are discussed to pave the way towards the rational design and applications of dopamine-based materials.
Topics: Dopamine; Nanostructures
PubMed: 34352605
DOI: 10.1016/j.cis.2021.102489 -
Schizophrenia Research Jul 2023The hypothesis of dopamine dysfunction in psychosis has evolved since the mid-twentieth century. However, clinical support from biochemical analysis of the transmitter...
BACKGROUND
The hypothesis of dopamine dysfunction in psychosis has evolved since the mid-twentieth century. However, clinical support from biochemical analysis of the transmitter in patients is still missing. The present study assessed dopamine and related metabolites in the cerebrospinal fluid (CSF) of first-episode psychosis (FEP) subjects.
METHODS
Forty first-episode psychosis subjects and twenty healthy age-matched volunteers were recruited via the Karolinska Schizophrenia Project, a multidisciplinary research consortium that investigates the pathophysiology of schizophrenia. Psychopathology, disease severity, and cognitive performance were rated as well as cerebrospinal fluid concentrations of dopamine and related metabolites were measured using a sensitive high-pressure liquid chromatography assay.
RESULTS
CSF dopamine was reliably detected in 50 % of healthy controls and in 65 % of first-episode psychosis subjects and significantly higher in first-episode psychosis subjects compared to age-matched healthy controls. No difference in CSF dopamine levels was observed between drug-naive subjects and subjects with short exposure to antipsychotics. The dopamine concentrations were positively associated with illness severity and deficits in executive functioning.
CONCLUSIONS
Dopamine dysfunction has long been considered a cornerstone of the pathophysiology of schizophrenia, although biochemical support for elevated brain dopamine levels has been lacking. The results of the present study, showing that FEP subjects have increased CSF dopamine levels that correlate to disease symptoms, should fill the knowledge gap in this regard.
Topics: Humans; Dopamine; Psychotic Disorders; Schizophrenia; Brain; Cognition
PubMed: 37271040
DOI: 10.1016/j.schres.2023.05.012 -
Proceedings of the National Academy of... May 2024Individual survival and evolutionary selection require biological organisms to maximize reward. Economic choice theories define the necessary and sufficient conditions,...
Individual survival and evolutionary selection require biological organisms to maximize reward. Economic choice theories define the necessary and sufficient conditions, and neuronal signals of decision variables provide mechanistic explanations. Reinforcement learning (RL) formalisms use predictions, actions, and policies to maximize reward. Midbrain dopamine neurons code reward prediction errors (RPE) of subjective reward value suitable for RL. Electrical and optogenetic self-stimulation experiments demonstrate that monkeys and rodents repeat behaviors that result in dopamine excitation. Dopamine excitations reflect positive RPEs that increase reward predictions via RL; against increasing predictions, obtaining similar dopamine RPE signals again requires better rewards than before. The positive RPEs drive predictions higher again and thus advance a recursive reward-RPE-prediction iteration toward better and better rewards. Agents also avoid dopamine inhibitions that lower reward prediction via RL, which allows smaller rewards than before to elicit positive dopamine RPE signals and resume the iteration toward better rewards. In this way, dopamine RPE signals serve a causal mechanism that attracts agents via RL to the best rewards. The mechanism improves daily life and benefits evolutionary selection but may also induce restlessness and greed.
Topics: Reward; Animals; Dopamine; Dopaminergic Neurons; Humans; Reinforcement, Psychology
PubMed: 38717856
DOI: 10.1073/pnas.2316658121 -
Nature Communications Oct 2022The lateral septum (LS) has been implicated in the regulation of locomotion. Nevertheless, the neurons synchronizing LS activity with the brain's clock in the...
The lateral septum (LS) has been implicated in the regulation of locomotion. Nevertheless, the neurons synchronizing LS activity with the brain's clock in the suprachiasmatic nucleus (SCN) remain unknown. By interrogating the molecular, anatomical and physiological heterogeneity of dopamine neurons of the periventricular nucleus (PeVN; A14 catecholaminergic group), we find that Th/Dat1 cells from its anterior subdivision innervate the LS in mice. These dopamine neurons receive dense neuropeptidergic innervation from the SCN. Reciprocal viral tracing in combination with optogenetic stimulation ex vivo identified somatostatin-containing neurons in the LS as preferred synaptic targets of extrahypothalamic A14 efferents. In vivo chemogenetic manipulation of anterior A14 neurons impacted locomotion. Moreover, chemogenetic inhibition of dopamine output from the anterior PeVN normalized amphetamine-induced hyperlocomotion, particularly during sedentary periods. Cumulatively, our findings identify a hypothalamic locus for the diurnal control of locomotion and pinpoint a midbrain-independent cellular target of psychostimulants.
Topics: Animals; Dopamine; Hypothalamus; Mice; Neurons; Somatostatin; Suprachiasmatic Nucleus
PubMed: 36209152
DOI: 10.1038/s41467-022-33584-3