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Current Opinion in Neurobiology Apr 2021Dopamine neurons have been intensely studied for their roles in reinforcement learning. A dominant theory of how these neurons contribute to learning is through the... (Review)
Review
Dopamine neurons have been intensely studied for their roles in reinforcement learning. A dominant theory of how these neurons contribute to learning is through the encoding of a reward prediction error (RPE) signal. Recent advances in dopamine research have added nuance to RPE theory by incorporating the ideas of sensory prediction error, distributional encoding, and belief states. Further nuance is likely to be added shortly by convergent lines of research on dopamine neuron diversity. Finally, a major challenge is to reconcile RPE theory with other current theories of dopamine function to account for dopamine's role in movement, motivation, and goal-directed planning.
Topics: Dopamine; Dopaminergic Neurons; Motivation; Reinforcement, Psychology; Reward
PubMed: 33197709
DOI: 10.1016/j.conb.2020.10.012 -
The American Journal of Psychiatry Nov 1991The initial hypothesis that schizophrenia is a manifestation of hyperdopaminergia has recently been faulted. However, several new findings suggest that abnormal,... (Review)
Review
OBJECTIVE
The initial hypothesis that schizophrenia is a manifestation of hyperdopaminergia has recently been faulted. However, several new findings suggest that abnormal, although not necessarily excessive, dopamine activity is an important factor in schizophrenia. The authors discuss these findings and their implications.
METHOD
All published studies regarding dopamine and schizophrenia and all studies on the role of dopamine in cognition were reviewed. Attention has focused on post-mortem studies, positron emission tomography, neuroleptic drug actions, plasma levels of the dopamine metabolite homovanillic acid (HVA), and cerebral blood flow.
RESULTS
Evidence, particularly from intracellular recording studies in animals and plasma HVA measurements, suggests that neuroleptics act by reducing dopamine activity in mesolimbic dopamine neurons. Post-mortem studies have shown high dopamine and HVA concentrations in various subcortical brain regions and greater than normal dopamine receptor densities in the brains of schizophrenic patients. On the other hand, the negative/deficit symptom complex of schizophrenia may be associated with low dopamine activity in the prefrontal cortex. Recent animal and human studies suggest that prefrontal dopamine neurons inhibit subcortical dopamine activity. The authors hypothesize that schizophrenia is characterized by abnormally low prefrontal dopamine activity (causing deficit symptoms) leading to excessive dopamine activity in mesolimbic dopamine neurons (causing positive symptoms).
CONCLUSIONS
The possible co-occurrence of high and low dopamine activity in schizophrenia has implications for the conceptualization of dopamine's role in schizophrenia. It would explain the concurrent presence of negative and positive symptoms. This hypothesis is testable and has important implications for treatment of schizophrenia and schizophrenia spectrum disorders.
Topics: Animals; Antipsychotic Agents; Brain; Cognition; Dopamine; Frontal Lobe; Homovanillic Acid; Humans; Receptors, Dopamine; Schizophrenia; Schizophrenic Psychology; Tomography, Emission-Computed
PubMed: 1681750
DOI: 10.1176/ajp.148.11.1474 -
Annual Review of Neuroscience 2007Many lesion studies report an amazing variety of deficits in behavioral functions that cannot possibly be encoded in great detail by the relatively small number of... (Review)
Review
Many lesion studies report an amazing variety of deficits in behavioral functions that cannot possibly be encoded in great detail by the relatively small number of midbrain dopamine neurons. Although hoping to unravel a single dopamine function underlying these phenomena, electrophysiological and neurochemical studies still give a confusing, mutually exclusive, and partly contradictory account of dopamine's role in behavior. However, the speed of observed phasic dopamine changes varies several thousand fold, which offers a means to differentiate the behavioral relationships according to their time courses. Thus dopamine is involved in mediating the reactivity of the organism to the environment at different time scales, from fast impulse responses related to reward via slower changes with uncertainty, punishment, and possibly movement to the tonic enabling of postsynaptic motor, cognitive, and motivational systems deficient in Parkinson's disease.
Topics: Animals; Behavior, Animal; Brain; Decision Making; Dopamine; Humans; Movement; Movement Disorders; Neural Pathways; Reward; Synaptic Transmission
PubMed: 17600522
DOI: 10.1146/annurev.neuro.28.061604.135722 -
Neuropharmacology 2009Dopamine is involved in drug reinforcement but its role in addiction is less clear. Here we describe PET imaging studies that investigate dopamine's involvement in drug... (Review)
Review
Dopamine is involved in drug reinforcement but its role in addiction is less clear. Here we describe PET imaging studies that investigate dopamine's involvement in drug abuse in the human brain. In humans the reinforcing effects of drugs are associated with large and fast increases in extracellular dopamine, which mimic those induced by physiological dopamine cell firing but are more intense and protracted. Since dopamine cells fire in response to salient stimuli, supraphysiological activation by drugs is experienced as highly salient (driving attention, arousal, conditioned learning and motivation) and with repeated drug use may raise the thresholds required for dopamine cell activation and signaling. Indeed, imaging studies show that drug abusers have marked decreases in dopamine D2 receptors and in dopamine release. This decrease in dopamine function is associated with reduced regional activity in orbitofrontal cortex (involved in salience attribution; its disruption results in compulsive behaviors), cingulate gyrus (involved in inhibitory control; its disruption results in impulsivity) and dorsolateral prefrontal cortex (involved in executive function; its disruption results in impaired regulation of intentional actions). In parallel, conditioning triggered by drugs leads to enhanced dopamine signaling when exposed to conditioned cues, which then drives the motivation to procure the drug in part by activation of prefrontal and striatal regions. These findings implicate deficits in dopamine activity-inked with prefrontal and striatal deregulation-in the loss of control and compulsive drug intake that results when the addicted person takes the drugs or is exposed to conditioned cues. The decreased dopamine function in addicted individuals also reduces their sensitivity to natural reinforcers. Therapeutic interventions aimed at restoring brain dopaminergic tone and activity of cortical projection regions could improve prefrontal function, enhance inhibitory control and interfere with impulsivity and compulsive drug administration while helping to motivate the addicted person to engage in non-drug related behaviors.
Topics: Animals; Brain; Diagnostic Imaging; Dopamine; Humans; Substance-Related Disorders
PubMed: 18617195
DOI: 10.1016/j.neuropharm.2008.05.022 -
Psychopharmacology Apr 2007Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: 'liking',... (Review)
Review
INTRODUCTION
Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: 'liking', learning, and 'wanting'. Does dopamine mostly mediate the hedonic impact of reward ('liking')? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli ('wanting')? Each hypothesis is evaluated here, and it is suggested that the incentive salience or 'wanting' hypothesis of dopamine function may be consistent with more evidence than either learning or 'liking'. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic 'liking' for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal 'wanting', and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive 'wanting' in addiction, but also provides opportunities for experiments to disentangle 'wanting', 'liking', and learning hypotheses. Results from studies that exploited those opportunities are described here.
CONCLUSION
In short, dopamine's contribution appears to be chiefly to cause 'wanting' for hedonic rewards, more than 'liking' or learning for those rewards.
Topics: Animals; Appetitive Behavior; Association Learning; Behavior, Addictive; Dopamine; Humans; Limbic System; Motivation; Neurotransmitter Agents; Nucleus Accumbens; Prosencephalon; Reinforcement, Psychology; Reward
PubMed: 17072591
DOI: 10.1007/s00213-006-0578-x -
Plant Signaling & Behavior Dec 2020Dopamine (3-hydroxytyramine or 3,4-dihydroxyphenethylamine) has many functions in animals, but also shows several other functions in plants. Since the discovery of... (Review)
Review
Dopamine (3-hydroxytyramine or 3,4-dihydroxyphenethylamine) has many functions in animals, but also shows several other functions in plants. Since the discovery of dopamine in plants in 1968, many studies have provided insight into physiological and biochemical functions, and stress responses of this molecule. In this review, we describe the biosynthesis of dopamine, as well as its role in plant growth and development. In addition, endogenous or exogenously applied dopamine improved the tolerance against several abiotic stresses, such as drought, salt, and nutrient stress. There are also several studies that dopamine contributes to the plant immune response against plant disease. Dopamine affects the expression of many abiotic stresses related genes, which highlights its role as a multi-regulatory molecule and can coordinate many aspects of plant development. Our review emphasized the effects of dopamine against environmental stresses along with future research directions, which will help improve the yield of eco-friendly crops and ensure food security.
Topics: Biosynthetic Pathways; Dopamine; Plant Development; Plants; Stress, Physiological
PubMed: 33040671
DOI: 10.1080/15592324.2020.1827782 -
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 -
Clinical Transplantation Jul 2018Renal-dose dopamine has fallen out of favor in the intensive care unit (ICU) during past years due to its ineffectiveness to prevent impending or to ameliorate overt... (Review)
Review
Renal-dose dopamine has fallen out of favor in the intensive care unit (ICU) during past years due to its ineffectiveness to prevent impending or to ameliorate overt renal failure in the critically ill. By contrast, growing evidence indicates that low-dose dopamine administered to the stable organ donor after brain death confirmation improves the clinical course of transplanted organs after kidney and heart transplantation. Ensuring a thorough monitoring for potential circulatory side effects, employment of dopamine at a dose of 4 μg/kg/min is safe in the deceased donor. Among recipients, the advantageous effect is easy to achieve, inexpensive, and devoid of adverse side effects. The mode of action relies on dopamine's propensity to mitigate injury in various cell systems from isolated transplantable organs under cold storage conditions. The present review article summarizes the clinical evidence of dopamine donor pretreatment in solid organ transplantation and focuses on the underlying molecular mechanisms of cellular protection. Introducing the routine use of low-dose dopamine for the management of the brain-dead donor in the ICU before procurement provides an evidence-based strategy to improve graft outcome after kidney transplantation without conferring harm to non-renal grafts, namely to livers and hearts, in cases of multi-organ donation.
Topics: Dopamine; Humans; Organ Preservation; Organ Transplantation; Primary Graft Dysfunction; Tissue and Organ Procurement
PubMed: 29790212
DOI: 10.1111/ctr.13292 -
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 -
Neuron Feb 2018Many learned responses depend on the coordinated activation and inhibition of synaptic pathways in the striatum. Local dopamine neurotransmission acts in concert with a... (Review)
Review
Many learned responses depend on the coordinated activation and inhibition of synaptic pathways in the striatum. Local dopamine neurotransmission acts in concert with a variety of neurotransmitters to regulate cortical, thalamic, and limbic excitatory inputs to drive the direct and indirect striatal spiny projection neuron outputs that determine the activity, sequence, and timing of learned behaviors. We review recent advances in the characterization of stereotyped neuronal and operant responses that predict and then obtain rewards. These depend on the local release of dopamine at discrete times during behavioral sequences, which, acting with glutamate, provides a presynaptic filter to select which excitatory synapses are inhibited and which signals pass to indirect pathway circuits. This is followed by dopamine-dependent activation of specific direct pathway circuits to procure a reward. These steps may provide a means by which higher organisms learn behaviors in response to feedback from the environment.
Topics: Animals; Behavior, Animal; Cerebral Cortex; Conditioning, Operant; Corpus Striatum; Dopamine; Neural Pathways; Neurons; Receptors, Dopamine D1; Receptors, Dopamine D2; Reward; Synapses
PubMed: 29420932
DOI: 10.1016/j.neuron.2018.01.006