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British Journal of Pharmacology Jan 2006Dopamine has moved from being an insignificant intermediary in the formation of noradrenaline in 1957 to its present-day position as a major neurotransmitter in the...
Dopamine has moved from being an insignificant intermediary in the formation of noradrenaline in 1957 to its present-day position as a major neurotransmitter in the brain. This neurotransmitter is involved in the control of movement and Parkinson's disease, the neurobiology and symptoms of schizophrenia and attention deficit hyperactivity disorder. It is also considered an essential element in the brain reward system and in the action of many drugs of abuse. This evolution reflects the ability of several famous names in neuropharmacology, neurology and psychiatry to apply new techniques to ask and answer the right questions. There is now excellent knowledge about the metabolism of dopamine, dopamine receptor systems and the structural organisation of dopamine pathways in the brain. Less is known about the function of the different receptors and how the various dopamine pathways are organised to produce normal behaviour, which exhibits disruption in the disease states mentioned. In particular, we have very limited information as to why and how the dopamine system dies or becomes abnormal in Parkinson's disease or a neurodevelopmental disorder such as schizophrenia. Dopamine neurones account for less than 1% of the total neuronal population of the brain, but have a profound effect on function. The future challenge is to understand how dopamine is involved in the integration of information to produce a relevant response rather than to study dopamine in isolation from other transmission systems. This integrated approach should lead to greater understanding and improved treatment of diseases involving dopamine.
Topics: Dopamine; History, 20th Century; History, 21st Century; Humans; Receptors, Dopamine; Schizophrenia; Substance-Related Disorders
PubMed: 16402097
DOI: 10.1038/sj.bjp.0706473 -
Brain Research Nov 2011Dopamine denervation gives rise to abnormal corticostriatal plasticity; however, its role in the symptoms and progression of Parkinson's disease (PD) has not been... (Review)
Review
Dopamine denervation gives rise to abnormal corticostriatal plasticity; however, its role in the symptoms and progression of Parkinson's disease (PD) has not been articulated or incorporated into current clinical models. The 'integrative selective gain' framework proposed here integrates dopaminergic mechanisms known to modulate basal ganglia throughput into a single conceptual framework: (1) synaptic weights, the neural instantiation of accumulated experience and skill modulated by dopamine-dependent plasticity and (2) system gain, the operating parameters of the basal ganglia, modulated by dopamine's on-line effects on cell excitability, glutamatergic transmission and the balance between facilitatory and inhibitory pathways. Within this framework and based on recent work, a hypothesis is presented that prior synaptic weights and established skills can facilitate motor performance and preserve function despite diminished dopamine; however, dopamine denervation induces aberrant corticostriatal plasticity that degrades established synaptic weights and replaces them with inappropriate, inhibitory learning that inverts the function of the basal ganglia resulting in 'anti-optimization' of motor performance. Consequently, mitigating aberrant corticostriatal plasticity represents an important therapeutic objective, as reflected in the long-duration response to levodopa, reinterpreted here as the correction of aberrant learning. It is proposed that viewing aberrant corticostriatal plasticity and learning as a provisional endophenotype of PD would facilitate investigation of this hypothesis.
Topics: Animals; Antiparkinson Agents; Basal Ganglia; Dopamine; Humans; Models, Biological; Parkinson Disease
PubMed: 22000081
DOI: 10.1016/j.brainres.2011.09.040 -
Critical Care Clinics Jul 1996In conclusion, dopamine has the unique ability, compared with other catecholamines, to improve renal blood flow, glomerular filtration rate, sodium excretion, and... (Review)
Review
In conclusion, dopamine has the unique ability, compared with other catecholamines, to improve renal blood flow, glomerular filtration rate, sodium excretion, and creatinine clearance, independent of its cardiac effects. In addition, low-dose dopamine can decrease renal and systemic vascular resistance, suppress aldosterone secretion, and interact with atrial natriuretic factor. Because of these clinically significant properties, dopamine has been used successfully to improve and treat acute oliguric renal failure in a variety of clinical situations as just described. In addition, there were no adverse or toxic cardiac effects, such as tachyarrhythmias or hypertension, detected with low-dose dopamine in studies reviewed for this publication. By increasing renal and mesenteric vasodilation, dopamine has been shown to be beneficial in preserving renal function in cardiac surgery, vascular surgery, liver transplantation, contrast-induced nephropathy, hypertension, and pediatric patients. A therapeutic renal effect has been observed in patients with hepatorenal syndrome or severe ovarian hyperstimulation syndrome, in patients requiring vasopressors and IABP, and in selected cases of acute oliguric renal failure and shock. Furthermore, the combination of low-dose dopamine with furosemide or prostaglandin results in enhanced renal effects. Further investigation is necessary to evaluate the important and specific therapeutic role of low-dose dopamine through prospective, randomized, double-blind studies. Until those data are available, the plethora of clinical evidence supporting the ability of low-dose dopamine to augment renal function continues to grow. For those who are skeptical, we offer the following suggestion: "The obscure we see eventually, the obvious takes a little longer"--E.R. Murrow.
Topics: Acute Kidney Injury; Critical Care; Critical Illness; Dopamine; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Humans; Receptors, Dopamine; Renal Circulation; Treatment Outcome
PubMed: 8839599
DOI: 10.1016/s0749-0704(05)70271-2 -
Journal of Neurochemistry Aug 2002Mesolimbic dopaminergic neurons modulate complex circuitry in the ventral forebrain involved in reward processing, although the precise function of the dopaminergic... (Review)
Review
Mesolimbic dopaminergic neurons modulate complex circuitry in the ventral forebrain involved in reward processing, although the precise function of the dopaminergic input is debated. Electrophysiological measurements have revealed that mesolimbic dopaminergic neurons can fire in either tonic or phasic modes, and that phasic firing accompanies the alerting or anticipatory phases of reward. However, the neurochemical relevance of this rapid neuronal discharge within the reward processing circuitry is not yet clear, in part because of difficulty in interpretation of extracellular dopamine measurements. Herein, the nature of the information provided by different neurochemical techniques is critically discussed. Classical methods of monitoring dopamine reveal changes in extracellular dopamine resulting from tonic neuronal activity, but do not have the temporal resolution to distinguish concentration transients. However, recent advances in dopamine sensors now enable transient dopamine concentrations resulting from phasic firing to be positively identified and followed on a physiologically relevant timescale. This has enabled demonstrations of discrete, phasic dopamine signals accompanying rewarding or alerting stimuli. Thus, enhanced dopamine release at terminals appears to be coincident with phasic electrical activity at cell bodies. These accumulating data promise to help unravel the precise role of phasic dopamine transmission in reward processing.
Topics: Animals; Dopamine; Electrochemistry; Extracellular Space; Humans; Limbic System; Microdialysis; Motivation; Neurons; Primates; Rats; Reward; Synaptic Transmission
PubMed: 12358778
DOI: 10.1046/j.1471-4159.2002.01005.x -
The Journal of Neuroscience : the... Feb 2016Initiating a reward-seeking behavior involves deciding on an action, how fast to initiate the action (initiation vigor), as well as how much effort to exert. These...
UNLABELLED
Initiating a reward-seeking behavior involves deciding on an action, how fast to initiate the action (initiation vigor), as well as how much effort to exert. These processes are thought to involve the mesolimbic dopamine system. Dopamine levels in the ventral striatum rise before initiating a reliably reinforced behavior. However, it is unknown whether dopamine is similarly involved with unreinforced actions (inactive lever presses, premature food port entries, insufficient number of active lever presses). Furthermore, does the dopamine response when initiating an action reflect specific aspects of motivated behavior, such as initiation vigor and exerted effort? Here, we analyzed voltammetry recordings of dopamine levels in the nucleus accumbens (NAcc) core and shell in rats working for food under a progressive ratio reinforcement schedule. We examined dopamine levels when rats initiated distinct actions (active lever presses, inactive lever presses, food port entries) that were temporally separated from cue- and reward-evoked dopamine release. Active lever pressing bouts were preceded by elevated dopamine release in the NAcc shell, as well as in the NAcc core, although only when rats exhibited high initiation vigor. Dopamine levels were transiently reduced in the NAcc core following an unreinforced food port entry and were unchanged throughout the NAcc when initiating inactive lever presses. The effort exerted and vigor to initiate a bout of active lever presses were signaled by dopamine transmission in the NAcc core, but not in the NAcc shell. These results demonstrate that the dopamine response when initiating a behavior is both region- and action-specific.
SIGNIFICANCE STATEMENT
Exogenous activation of the mesolimbic dopamine system facilitates motivated behavior. However, a direct relationship has not been established between endogenous phasic dopamine transmission and measures of motivation, such as the vigor to initiate an action and the effort exerted in a bout of activity. The present work demonstrates that the dopamine response when initiating an action depends both upon where dopamine is released and what action is performed. Furthermore, dopamine reflects measures of motivated behavior selectively within the nucleus accumbens core.
Topics: Animals; Conditioning, Operant; Cues; Dopamine; Food; Male; Motivation; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Reward; Synaptic Transmission
PubMed: 26888930
DOI: 10.1523/JNEUROSCI.1279-15.2016 -
Cortex; a Journal Devoted To the Study... Oct 2012Fundamental advances in neuroscience have come from investigations into neuroplasticity and learning. These investigations often focus on identifying universal... (Review)
Review
Fundamental advances in neuroscience have come from investigations into neuroplasticity and learning. These investigations often focus on identifying universal principles across different individuals of the same species. Increasingly, individual differences in learning success have also been observed, such that any seemingly universal principle might only be applicable to a certain extent within a particular learner. One potential source of this variation is individuals' genetic differences. Adult language learning provides a unique opportunity for understanding individual differences and genetic bases of neuroplasticity because of the large individual differences in learning success that have already been documented, and because of the body of empirical work connecting language learning and neurocognition. In this article, we review the literature on the genetic bases of neurocognition, especially studies examining polymorphisms of dopamine (DA)-related genes and procedural learning. This review leads us to hypothesize that there may be an association between DA-related genetic variation and language learning differences. If this hypothesis is supported by future empirical findings we suggest that it may point to neurogenetic markers that allow for language learning to be personalized.
Topics: Animals; Dopamine; Humans; Individuality; Language; Language Development; Learning; Neuronal Plasticity
PubMed: 22565204
DOI: 10.1016/j.cortex.2012.03.017 -
The Biological Bulletin Dec 2020AbstractThe catecholamine 3,4-dihydroxyphenethylamine, or dopamine, acts as a neurotransmitter across a broad phylogenetic spectrum. Functions attributed to dopamine in... (Review)
Review
AbstractThe catecholamine 3,4-dihydroxyphenethylamine, or dopamine, acts as a neurotransmitter across a broad phylogenetic spectrum. Functions attributed to dopamine in the mammalian brain include regulation of motor circuits, valuation of sensory stimuli, and mediation of reward or reinforcement signals. Considerable evidence also supports a neurotransmitter role for dopamine in gastropod molluscs, and there is growing appreciation for its potential common functions across phylogeny. This article reviews evidence for dopamine's transmitter role in the nervous systems of gastropods. The functional properties of identified dopaminergic neurons in well-characterized neural circuits suggest a hypothetical incremental sequence by which dopamine accumulated its diverse roles. The successive acquisition of dopamine functions is proposed in the context of gastropod feeding behavior: (1) sensation of potential nutrients, (2) activation of motor circuits, (3) selection of motor patterns from multifunctional circuits, (4) valuation of sensory stimuli with reference to internal state, (5) association of motor programs with their outcomes, and (6) coincidence detection between sensory stimuli and their consequences. At each stage of this sequence, it is proposed that existing functions of dopaminergic neurons favored their recruitment to fulfill additional information processing demands. Common functions of dopamine in other intensively studied groups, ranging from mammals and insects to nematodes, suggest an ancient origin for this progression.
Topics: Animals; Dopamine; Gastropoda; Mollusca; Neurotransmitter Agents; Phylogeny
PubMed: 33347799
DOI: 10.1086/711293 -
ACS Chemical Neuroscience Jan 2015Survival is dictated by an organism's fitness in approaching positive stimuli and avoiding harm. While a rich literature outlines a role for mesolimbic dopamine in... (Review)
Review
Survival is dictated by an organism's fitness in approaching positive stimuli and avoiding harm. While a rich literature outlines a role for mesolimbic dopamine in reward and appetitive behaviors, dopamine's involvement in aversion and avoidance behaviors remains controversial. Debate surrounding dopamine's function in the processing of negative stimuli likely stems from conflicting results reported by single-unit electrophysiological studies. Indeed, a number of studies suggest that midbrain dopaminergic cells are inhibited by the presentation of negative or fearful stimuli, while others report no change, or even an increase, in their activity. These disparate results may be due to population heterogeneity. Recent evidence demonstrates that midbrain dopamine neurons are heterogeneous in their projection targets, responses to environmental stimuli, pharmacology, and influences on motivated behavior. Thus, in order to assemble an accurate account of dopamine function during aversive stimulus experience and related behavior, it is necessary to examine the functional output of dopamine neural activity at mesolimbic terminal regions. This Review presents a growing body of evidence that dopamine release in the nucleus accumbens encodes not only reward, but also aversion. For example, our laboratory recently utilized fast-scan cyclic voltammetry to show that real-time changes in accumbal dopamine release are detected when animals are presented with predictors of aversion and its avoidance. These data, along with other reports, support a considerably more nuanced view of dopamine neuron function, wherein accumbal dopamine release is differentially modulated by positive and negative affective stimuli to promote adaptive behaviors.
Topics: Action Potentials; Animals; Databases, Factual; Dopamine; Escape Reaction; Humans; Motivation; Neurochemistry; Neurons; Nucleus Accumbens
PubMed: 25491156
DOI: 10.1021/cn500255p -
Cells Jan 2019Parkinson's disease, like other neurodegenerative diseases, exhibits two common features: Proteinopathy and oxidative stress, leading to protein aggregation and... (Review)
Review
Parkinson's disease, like other neurodegenerative diseases, exhibits two common features: Proteinopathy and oxidative stress, leading to protein aggregation and mitochondrial damage respectively. Because both protein aggregates and dysfunctional mitochondria are eliminated by autophagy, we suggest that inadequate clearance may couple the two phenomena. If a neuron's autophagy machinery is overwhelmed, whether by excessive oxidative stress or by excessive protein aggregation, protein aggregates and dysfunctional mitochondria will both accumulate. Parkinson's disease may provide a unique window into this because there is evidence that both sides contribute. Mutations amplifying the aggregation of α-synuclein are associated with Parkinson's disease. Likewise, mutations in Parkin and PINK1, proteins involved in mitophagy, suggest that impaired mitochondrial clearance is also a contributing factor. Many have suggested that dopamine oxidation products lead to oxidative stress accounting for the dopaminergic selectivity of the disease. We have presented evidence for the specific involvement of hypochlorite-oxidized cysteinyl-dopamine (HOCD), a redox-cycling benzothiazine derivative. While toxins like 6-hydroxydopamine and 1-methyl-4-phenyl pyridinium (MPP+) have been used to study mitochondrial involvement in Parkinson's disease, HOCD may provide a more physiologically relevant approach. Understanding the role of mitochondrial dysfunction and oxidative stress in Parkinson's disease and their relation to α-synuclein proteinopathy is important to gain a full picture of the cause, especially for the great majority of cases which are idiopathic.
Topics: Autophagy; Dopamine; Humans; Mitochondria; Mitophagy; Oxidative Stress; Proteins
PubMed: 30654525
DOI: 10.3390/cells8010059 -
Frontiers in Bioscience (Elite Edition) Jun 2013The last sixty years of research has provided extraordinary advances of our knowledge of the reward system. Since its discovery as a neurotransmitter by Carlsson and... (Review)
Review
The last sixty years of research has provided extraordinary advances of our knowledge of the reward system. Since its discovery as a neurotransmitter by Carlsson and colleagues (1), dopamine (DA) has emerged as an important mediator of reward processing. As a result, a number of electrochemical techniques have been developed to measure DA in the brain. Together, these techniques have begun to elucidate the complex roles of tonic and phasic DA signaling in reward processing and addiction. In this review, we will first provide a guide for the most commonly used electrochemical methods for DA detection and describe their utility in furthering our knowledge about DA's role in reward and addiction. Second, we will review the value of common in vitro and in vivo preparations and describe their ability to address different types of questions. Last, we will review recent data that has provided new mechanistic insight of in vivo phasic DA signaling and its role in reward processing and reward-mediated behavior.
Topics: Animals; Brain; Dopamine; Electrochemical Techniques; Motivation; Signal Transduction
PubMed: 23747914
DOI: 10.2741/e678