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Astrocytic D1 Dopamine-Signaling Regulates Synaptic Remodeling and Cocaine Seeking.

D1-type receptor (D1R)-mediated dopaminergic signaling within the nucleus accumbens shell (NAcSh) is essential for forming adaptive circuit changes that embed persistent memories associated with drug seeking and craving. While D1R is expressed in both NAcSh neurons and astrocytes, the specific contribution of astrocytic D1R to drug-related circuit plasticity remains poorly understood. Here, we demonstrate in mouse NAcSh slices that D1R agonists increase astrocytic Ca 2+ activity, an effect that is attenuated by astrocyte-specific D1R knockdown. Furthermore, selective knockdown of astrocytic D1…

Hippo signaling regulates cuticle pigmentation and dopamine metabolism in Drosophila.

Pigmentation plays multiple important roles in development, physiology and evolution. Melanization of the insect cuticle requires dopamine as a precursor of melanin and involves key enzymes in dopamine biosynthesis including Tyrosine hydroxylase (TH) and Dopa decarboxylase (Ddc). Some studies have hinted that disruption of the evolutionarily conserved Hippo signaling pathway, which has been primarily studied in the context of tissue growth, may lead to changes in cuticle pigmentation in the fruit fly Drosophila melanogaster. However, to our knowledge, there have not been any systematic investi…

Parkinsonism Exacerbation due to Acute Dopamine Depletion: A Conundrum Revisited.

BACKGROUND: Fever and worsening rigidity in Parkinson's disease (PD) may resemble neuroleptic malignant syndrome (NMS). We examined PD patie … in carbidopa-levodopa, 7% (1/15) had sepsis alone, 33% (5/15) were exposed to new or increased antidopaminergic drugs, and 7% (1/15) had deep brain stimulator (DBS) malfunction. LITERATURE REVIEW: Several terms to describe exacerbation of parkinsonism including NMS-like state and parkinsonism hyperpyrexia syndrome (PHS) have been proposed over the years …

Altered Retinal Dopamine Homeostasis in Murine Models of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of currently untreatable inherited retinal degenerations that share similar disease manifestations despite distinctive genetic causes. Dopamine (DA) is an important and tightly regulated catecholaminergic neurotransmitter required for multiple modulatory functions throughout the central nervous system, including the retina. Dysregulation of DA homeostasis has been reported during neurodegeneration, but how it is regulated in RP remains poorly understood. Here, we demonstrate that early RP is associated with marked dysregulation of the dopamine…

Allometry correction in semi-quantitative analysis of dopamine transporter SPECT.

BACKGROUND: Striatal specific binding ratios (SBR) are widely used to support the interpretation of dopamine transporter SPECT scans. Automatic SBR computation often involves using affine transformations to map the individual SPECT images to an anatomical reference space for ROI analysis using predefined standard masks. This does not account for differences in volumetric scaling between brain structures since, by definition, affine transformations preserve volume ratios. However, striatal volume has been reported to scale proportional to (intracranial volume)0.4, indicating particularly pronou…

Prospective contingency explains behavior and dopamine signals during associative learning.

Associative learning depends on contingency, the degree to which a stimulus predicts an outcome. Despite its importance, the neural mechanisms linking contingency to behavior remain elusive. In the present study, we examined the dopamine activity in the ventral striatum-a signal implicated in associative learning-in a Pavlovian contingency degradation task in mice. We show that both anticipatory licking and dopamine responses to a conditioned stimulus decreased when additional rewards were delivered uncued, but remained unchanged if additional rewards were cued. These results conflict with con…

Chronic inflammatory pain suppresses alcohol intake and accumbal dopamine response.

Alcohol use disorders (AUDs) are influenced by factors that initiate, maintain, and/or induce relapse. Chronic pain is both a risk factor for and consequence of AUD, sharing neurological pathways that affect the mesolimbic dopaminergic system. This study examines how inflammatory pain impacts long-term alcohol intake and mesolimbic dopamine transmission in alcohol-naïve rats. Inflammatory pain was induced in eight-week-old Sprague Dawley rats using complete Freund adjuvant (CFA), while controls received saline. Two protocols were followed: one group had continuous access to 20 % ethanol for on…

Discovering next-generation dopamine transporter drugs with lower abuse potential.

Many traditional psychostimulants used to treat neuropsychiatric disorders by targeting the dopamine transporter (DAT) exhibit a high potential of abuse. This necessitates the development of next-generation drugs with improved safety. Discovering atypical DAT inhibitors represent a promising strategy that may be facilitated by integration of structural pharmacology and artificial intelligence.

Dopamine-modified hyaluronic acid hydrogel's role in spinal cord injury.

Spinal cord injury (SCI) is one of the most severe diseases in the world caused by violence or accidents, often leading to the loss of sensation, movement, and autonomic nervous function, resulting in a high rate of disability. Current clinical treatment strategies often fail to meet expectations. Here, we designed a dopamine (DP)-modified hyaluronic acid (HA) hydrogel combined with neurotrophic factors (NGF) to improve the adverse microenvironment after spinal cord injury (SCI) and promote axonal regeneration. HA, as a "scaffolding molecule," utilizes the reaction between 1-ethyl-(3-dimethyla…

Системная гипотеза о диспропорции дофамина в ранних множественных склерозах.

Множественный склероз (MS) — хроническое аутоиммунное расстройство центральной нервной системы, при этом имеются данные, свидетельствующие о том, что возрастные изменения мозга могут повлиять на его развитие. Клинический изолированный синдром (CIS) часто обозначает раннюю фазу MS, при этом в качестве симптома часто проявляется оптический неврит. Несмотря на признание в качестве одного из первых показателей, механизмы воздействия оптического неврита и его вклад в продвижение НР остаются неясными. Традиционно иммунное воспаление доминировало в исследованиях MS; однако, появляющиеся данные свидет

Совпадение в аннотации оригинала
Multiple Sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, with evidence suggesting that age-related brain chan … research; however, emerging evidence highlights neurotransmitter dysregulation-especially involving dopamine-as a crucial factor in disease pathophysiology. The impact of dopamine imbalance on neural circuits and its role in advancing MS requires further investigation. This paper proposes a system-level, dopamine-based hypothesis to explain MS origins, foc …

Breast Cancer risk in patients with dopamine agonist-treated hyperprolactinemia.

PURPOSE: Given prolactin's (PRL) multifaceted roles in mammary tissue, an association between hyperprolactinemia and breast cancer has been hypothesized. Despite previous studies not identifying this risk, we aimed to investigate whether a connection exists. METHODS: This retrospective cohort study compared breast cancer incidence in patients with dopamine agonist (DA)-treated hyperprolactinemia versus matched controls in a 1:5 ratio. The primary outcome was a breast cancer diagnosis following hyperprolactinemia diagnosis. RESULTS: The cohort consisted of 1484 female patients with DA-treated…

Impact of 5-Lipoxygenase Deficiency on Dopamine-Mediated Behavioral Responses.

The 5-lipoxygenase/leukotriene system has been implicated in both physiological and pathological states within the central nervous system. Understanding how this system interacts with the dopaminergic system could provide valuable insights into dopamine-related pathologies. This study focused on examining both motor and non-motor dopamine-related responses in 5-lipoxygenase/leukotriene-deficient mice. We used pharmacological agents such as amphetamine, apomorphine, and reserpine to challenge the dopaminergic system, evaluating their effects on prepulse inhibition reaction (PPI), general motor …

Multifunctional Dopamine-Based Hydrogel Microneedle Electrode for Continuous Ketone Sensing.

Diabetic ketoacidosis (DKA), a severe complication of type 1 diabetes (T1D), is triggered by production of large quantities of ketone bodies, requiring patients with T1D to constantly monitor their ketone levels. Here, a skin-compatible hydrogel microneedle (HMN)-continuous ketone monitoring (HMN-CKM) device is reported. The sensing mechanism relies on the catechol-quinone chemistry inherent to the dopamine (DA) molecules that are covalently linked to the polymer structure of the HMN patch. The DA serves the dual-purpose of acting as a redox mediator for measuring the byproduct of oxidation of…

Striatal dopamine transporter uptake, parkinsonism and cognition in Alzheimer's disease.

BACKGROUND AND PURPOSE: The correlates of motor parkinsonism in Alzheimer's disease (AD) remain controversial. The effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD were evaluated. METHODS: This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography, 18 F-florbetaben positron emission tomography, 3 T brain magnetic resonance imaging, and Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The…

Dopamine alters phage morphology to exert an anti-infection effect.

Antiviral drug development is important for human health, and the emergence of novel COVID-19 variants has seriously affected human lives and safety. A bacteriophage-a bacterial virus with a small and simple structure-is an ideal experimental candidate for studying the interactions between viruses and their hosts. In this study, the effects and mechanisms of catecholamines on phages were explored, and dopamine (DA) was found to have general and efficient anti-infection effects. A clear dose-dependent effect was observed when different phages were treated with DA, with higher DA concentrations …

Efficient mercury(II) removal by corn bract/dopamine@ZnS composites.

In this study, we have utilized corn bract, a green agricultural by-product, as a carrier. It is subsequently modified with zinc sulfide to synthesize an efficient composite material termed as corn bract/polydopamine@zinc sulfide (CB/PDA@ZnS). This novel composite demonstrates significant potential for biomass removal of mercury ions (Hg(II)). The composition, structure, and morphology of CB/PDA@ZnS composites are characterized by Fourier transform infrared (FT-IR) spectrum, thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), and scanning electron microscope (SEM). The effect of …

Gastrointestinal Symptoms and Dopamine Transporter Asymmetry in Early Parkinson's Disease.

BACKGROUND: The neurophysiological correlates of gastrointestinal symptoms (GISs) in Parkinson's disease (PD) are not well understood. It has been proposed that in patients with a gastrointestinal origin of PD dopaminergic neurodegeneration would be more symmetric. OBJECTIVES: The aim is to assess the associations between GISs and asymmetry of nigrostriatal dopaminergic neurodegeneration in PD. METHODS: Ninety PD patients were assessed using motor and GIS scales and 123 I-FP-CIT SPECT. We calculated the asymmetry index and the predominant side of motor symptoms and dopamine transporter (DAT)…

Metabolic effects of dopamine-agonists treatment among patients with prolactinomas.

PURPOSE: To evaluate the effect of cabergoline treatment on metabolic parameters including the Triglyceride-glucose (TyG) index in newly diagnosed patients with prolactinoma. METHODS: 71 consecutive nondiabetic patients with prolactinoma were enrolled. Anthropometric and laboratory tests including TyG index were measured at baseline, 3 and 6 months visits. Treatment with cabergoline at the dose of 0.25 mg twice weekly was started and increased according to prolactin levels and continued for 6 months. RESULTS: At the baseline examination, the mean (SD) age, body mass index (BMI), waist circum

Noradrenaline activation of hippocampal dopamine D1 receptors promotes antidepressant effects.

Dopamine D1 receptors (D1Rs) in the hippocampal dentate gyrus (DG) are essential for antidepressant effects. However, the midbrain dopaminergic neurons, the major source of dopamine in the brain, only sparsely project to DG, suggesting possible activation of DG D1Rs by endogenous substances other than dopamine. We have examined this possibility using electrophysiological and biochemical techniques and found robust activation of D1Rs in mouse DG neurons by noradrenaline. Noradrenaline at the micromolar range potentiated synaptic transmission at the DG output and increased the phosphorylation of…

Does dopamine deficiency affect sex-dependent prognosis in Parkinson's disease?

INTRODUCTION: A bundle of evidence indicates that biological sex is an important factor for clinical phenotypes as well as prognosis in Parkinson's disease (PD). We investigated the effect of nigrostriatal dopaminergic degeneration on longitudinal outcomes according to sex in patients with PD. METHODS: We recruited 571 consecutive drug-naïve PD patients (279 men and 292 women) who were followed up for ≥2 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging. A Cox proportional hazard model was used to compare the risk of developing levodopa-induced dyski…