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Determination of dopamine and dopamine-derived (R)-/(S)-salsolinol and norsalsolinol in various human brain areas using solid-phase extraction and gas chromatography/mass spectrometry.

Using a solid-phase extraction procedure and a gas chromatographic-mass spectrometric (GC/MS) method the levels of dopamine and the levels of dopamine-derived salsolinol (SAL) and norsalsolinol (NorSAL) were determined in human brain areas involved in the etiology of alcoholism, parkinsonism and other diseases. The possibility that biosynthesis of salsolinol occurs through a stereospecific enzymatic reaction was considered. Using a two-step derivatization with N-methyl-N-trimethylsilyltrifluoracetamide (MSTFA) and the chiral reagent (R)-(-)-2-phenylbutyryl chloride, baseline separated peaks of…

Dopamine agonist-induced locomotor activity in rats treated with 6-hydroxydopamine at differing ages: functional supersensitivity of D-1 dopamine receptors in neonatally lesioned rats.

Locomotor responses caused by dopamine receptor agonists with presumed specificity for D-1 or D-2 receptor subtypes were compared to apomorphine-induced locomotion in neonatally and adult 6-hydroxydopamine (6-OHDA)-treated rats. In adult 6-OHDA-treated rats, apomorphine and the D-2 agonist, LY-171555, produced a marked, dose-related increase in locomotor activity. Increases in locomotion observed in neonatally 6-OHDA-treated rats after apomorphine and LY-171555 administration were less than one-third of those seen in rats treated as adults with 6-OHDA. Neonatally 6-OHDA-treated rats, positive …

Glucose-Dependent Insulinotropic Polypeptide Receptors Are Expressed in the Lateral Septum and Reduce Electrically-Evoked Dopamine Release as well as the Ability of Cocaine to Increase Extracellular Dopamine.

Tirzepatide, a dual agonist of the glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR), represents a new class of medication for obesity and type II diabetes treatment. Using laboratory mice, we show that GIPRs are present in the lateral septum (LS) in cells also expressing GLP-1R, particularly in the dorsolateral LS. Likewise, we show the coexpression of the dopamine (DA) D2 receptor (DRD2) in LS cells with GLP-1R in both the dorsolateral and intermediate portions of the LS. Using fast-scan cyclic voltammetry, we demonstrate that systemic…

Cinnarizine, a Calcium Channel Blocker, Partially Prevents the Striatal Dopamine Decline and Loss of Nigral Dopamine Neurons in the Lactacystin-Induced Rat Model of Parkinson's Disease.

Selective proteasome inhibitors, used to model Parkinsonian-like pathology, are known to disrupt calcium homeostasis, but the role of calcium ions in dopaminergic neuron degeneration remains unclear. The present in vivo study examined the effects of a 7-day intraperitoneal administration of cinnarizine (10 or 30 mg/kg), a voltage-gated calcium channel blocker, in rats unilaterally injected into the substantia nigra compacta (SNc) with lactacystin (Lac; 1 µg/2 µL) or vehicle. Dopamine (DA) and its metabolites were quantified in striatal homogenates via high-performance liquid chromatography. Th…

Comparison of phosphodiesterase 10A, dopamine receptors D1 and D2 and dopamine transporter ligand binding in the striatum of the R6/2 and BACHD mouse models of Huntington's disease.

BACKGROUND: Phosphodiesterase 10A (PDE10A) is expressed at high levels in the striatum and has been proposed both as a biomarker for Hunting … binding was compared to binding of known markers of striatal atrophy in Huntington's disease, e.g. dopamine transporter (DAT) and dopamine receptors D1 and D2. RESULTS: We found that in the R6/2 model at 6 weeks of age, mice showed high variability of binding, however binding of all ligands was significantly decreased at 8 and 12 weeks of age. In contras …

Effects of acute and chronic systemic administration of some typical antipsychotic drugs on turnover of dopamine and potassium ion-induced release of dopamine in the striatum of the rat in vivo.

Chronoamperometry was used to measure the dose dependency of antipsychotic drug (spiperone, haloperidol and chlorpromazine)-induced increases in depolarization-stimulated release of dopamine in the striatum of the rat in vivo. The dose-response curves were found to be at least biphasic (small doses increased release and large doses inhibited release) and different in shape from dose-response curves for increases in the turnover of dopamine, suggesting that the two processes may not be related. The threshold dose to induce increased depolarization-stimulated release of dopamine correlated with …

Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation.

Psychomotor retardation, defined as generalized slowing of movement and speech, is a feature of several neurological and psychiatric disorders. In this review, we discuss the hypothesis that reduced striatal dopaminergic transmission is a transdiagnostic substrate for psychomotor retardation underlying the motor features of conditions such as Parkinson's disease, drug-induced parkinsonism, neuroleptic malignant syndrome, catatonia and depression. We examine the evidence across clinical, epidemiological, neuroimaging, laboratory and therapeutic studies. Parkinsonian disorders share slowed movem…

Differences in the Effect of Dopamine on the Phototransduction Between Lampreys and Jawed Vertebrates.

Dopamine is one of the most important neurotransmitters for regulating retinal function and adjusting vision to the diurnal cycle. It exerts its regulatory effects, in part, through the cAMP pathway. Previous studies have demonstrated that dopamine affects phototransduction in amphibian rods, and that elevated intracellular levels of cAMP modulate the function of vertebrate rods and cones. Lamprey, the most primitive vertebrate, could be valuable for studying the evolution of dopamine regulatory loops in the retina. We examined whether the photoresponse properties of long (cone-like) and short…

Tau Accumulation and Dopamine Transporter Availability in Elderly Adults with Depression.

BACKGROUND: Depression in later life is associated with dopaminergic dysfunction and increased risk of neurodegenerative disorders, although the relationship between dopamine transporter (DAT) availability and tau accumulation remains unclear. Although previous studies have linked tau and DAT in neurodegenerative diseases, evidence related to depression is limited. Therefore, this study used positron emission tomography (PET) to investigate the association between tau pathology and DAT availability in elderly adults with depression. METHODS: Six patients diagnosed with depression according to…

Dopamine alters motor learning performance in the presence and absence of feedback.

We often choose to learn motor skills not only because of some external reward, but also because motor learning, in and of itself, is satisfying. While dopamine is thought to drive reward-based motor learning, it remains unclear whether dopamine is implicated in motor learning under conditions ostensibly driven by intrinsic rewards/motivation (i.e., in the absence of extrinsic feedback or reward). Here, by pharmacologically manipulating dopamine using the dopamine precursor Levodopa, we investigated the role of dopamine in an explicit motor learning task guided by internally determined signals…

The effects of increasing and decreasing dopamine on inhibition of return: a psychopharmacological investigation.

Inhibition of Return (IOR) is the phenomenon of being slower to re-attend to previously attended locations, and is thought to improve the efficiency of attention. Previous studies of dopaminergic disorders indicate that excessive or insufficient dopamine signaling in the striatum of the brain reduces IOR magnitude. However, there have been no studies of the direct effects of dopamine depletion on IOR in healthy individuals, or that have compared the effect of dopamine increases and decreases within the same population. Therefore, in the present study, we administered a selective dopamine-2 rec…

Retention and Distribution of Dopamine-Dependent Reward Memory in Regenerating Planaria.

Memory is generally thought to be stored within centralized neural circuits. However, whether learned behaviors can persist in the absence o … stored even outside the cephalic nervous system. As a secondary objective, we examined the role of dopaminergic reinforcement using a D1 dopamine receptor antagonist during training. While antagonist-treated planaria failed to develop a CPP, posterior fragments from these amputated planaria likewise showed no conditioned preference, indicating that dopami …

Мезокортическая дофаминовая гипофункция и префронтальный дефицит пластичности в модели капризоны.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы, часто связанное с когнитивным расстройством, которое в решающей степени зависит от целостности префронтальной коры (PFC) и ее мезокорных допаминергических вводимых ресурсов. Однако прямые экспериментальные данные, связывающие дофронтальную дисфункцию дофамина с когнитивными дисфункциями, связанными с MS, ограничены. Здесь мы изучили вклад мезокортической допаминергической передачи в когнитивные и поведенческие изменения с использованием модели кухонной зоны обезвоживания у самцов крыс Вистар. После

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system frequently associated with cognitive impairment, which critically depends on the integrity of the prefrontal cortex (PFC) and its mesocortical dopaminergic inputs. However, direct experimental evidence linking prefrontal dopamine dysfunction to MS-related co…

Dopamine stabilized in ultra-nanoreservoirs for controlled delivery in parkinson's disease.

AIMS: Parkinson's disease (PD) is a neurodegenerative disorder caused by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to impaired dopamine (DA) signaling and motor control. Intermittent dosing of current DA precursors results in side effects, prompting research into controlled drug release mechanisms for sustained and targeted delivery of DA. MATERIALS & METHODS: In this work, we stabilized DA within a nanostructured silicate matrix (nanoreservoir) using the sol-gel method. We examined the physicochemical properties, kinetics of drug rele…

New insights into axonal regulators of dopamine transmission in health and disease.

Dopamine release in the striatum is credited with being critical to the selection and learning of motivated actions and outcomes. Dysregulation of striatal dopamine release underlies multiple disorders of action selection and reward-processing, such as Parkinson's disease, schizophrenia and addiction disorders, and is a major target for therapeutic interventions. The axonal molecular and circuit mechanisms governing dopamine exocytosis are incompletely resolved, but accumulating evidence suggests some key points of divergence from canonical neurotransmitter synapses. In this review, we bring t…

Choroidal thickening and retinal dopamine increase in mice at high altitude.

The mechanisms underlying the low incidence of myopia at high altitudes remain unclear. Choroidal thickness and the dopaminergic system have been shown to be closely associated with myopia development. This study aimed to investigate the effects of high altitude exposure on choroidal thickness and the dopaminergic system. Mice were subjected to acute hypobaric hypoxia at an altitude of 5000 m for durations ranging from 2 to 72 h, as well as chronic exposure at an altitude of 3670 m for a period of 3 months. Choroidal thickness was assessed using hematoxylin and eosin (H&E) staining of ocular t…

Dopamine and Lysine Modified Polyimide Fibers for Antithrombosis and Endothelialization Studies.

Small-diameter vascular grafts (SDVGs, <6 mm) exhibit significant potential as alternatives to coronary and peripheral arteries, yet their clinical application is hindered by thrombosis and intimal hyperplasia. A synergistic modification strategy utilizing polydopamine (PDA) and lysine (Lys) was developed to functionalize polyimide (PI) fibers, aiming to enhance the antithrombotic properties and endothelial regeneration capacity of SDVGs. Alkaline etching activates PI fibers and facilitates the formation of PDA-Lys composite coatings through Schiff base and Michael addition reactions. Characte…

Pulmonary Fibrosis in a Patient With a Prolactinoma on Dopamine Agonists: Coincidence or Consequence.

Prolactinomas are the most common functional pituitary tumor and are typically managed with dopamine agonists such as bromocriptine or cabergoline. Although these agents are generally well tolerated and effective in reducing prolactin levels and often tumor size, they have been implicated in rare but serious fibrotic complications, including interstitial lung disease (ILD). We describe a 65-year-old man with a longstanding prolactinoma who received cumulative high-dose bromocriptine and cabergoline therapy over several decades. Despite initial tumor shrinkage and partial biochemical control of…

Dopamine and its effects on the respiratory system: A narrative literature review.

Dopamine is a neuromodulator molecule that is involved in several systems in the human body. As a neurotransmitter, it plays a role in regulating reward, pleasure, and motor control in the brain. Beyond its well-known central nervous system functions it significantly influences peripheral systems including kidneys, circulatory system, and notably, immune system. It increases glomerular filtration rate and renal blood flow in the kidneys, while it increases aortic pressure and cardiac output in the circulatory system. Crucially, dopamine and its receptors have been identified on various immune …

Examining the role of the photopigment melanopsin in the striatal dopamine response to light.

The mesolimbic dopamine system is a set of subcortical brain circuits that plays a key role in reward processing, reinforcement, associative learning, and behavioral responses to salient environmental events. In our previous studies of the dopaminergic response to salient visual stimuli, we observed that dopamine release in the lateral nucleus accumbens (LNAc) of mice encoded information about the rate and magnitude of rapid environmental luminance changes from darkness. Light-evoked dopamine responses were rate-dependent, robust to the time of testing or stimulus novelty, and required phototr…