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Nature Neuroscience Jun 2018Dopamine is a critical modulator of both learning and motivation. This presents a problem: how can target cells know whether increased dopamine is a signal to learn or... (Review)
Review
Dopamine is a critical modulator of both learning and motivation. This presents a problem: how can target cells know whether increased dopamine is a signal to learn or to move? It is often presumed that motivation involves slow ('tonic') dopamine changes, while fast ('phasic') dopamine fluctuations convey reward prediction errors for learning. Yet recent studies have shown that dopamine conveys motivational value and promotes movement even on subsecond timescales. Here I describe an alternative account of how dopamine regulates ongoing behavior. Dopamine release related to motivation is rapidly and locally sculpted by receptors on dopamine terminals, independently from dopamine cell firing. Target neurons abruptly switch between learning and performance modes, with striatal cholinergic interneurons providing one candidate switch mechanism. The behavioral impact of dopamine varies by subregion, but in each case dopamine provides a dynamic estimate of whether it is worth expending a limited internal resource, such as energy, attention, or time.
Topics: Animals; Dopamine; Dopaminergic Neurons; Humans; Learning; Motivation; Signal Transduction
PubMed: 29760524
DOI: 10.1038/s41593-018-0152-y -
Current Opinion in Neurobiology Aug 2019Dopamine controls motor functions, motivation, and reward-related learning through G-protein coupled receptor signaling. The current working model is that upon release,... (Review)
Review
Dopamine controls motor functions, motivation, and reward-related learning through G-protein coupled receptor signaling. The current working model is that upon release, dopamine diffuses to influence many target cells via wide-spread receptors. Recent studies, however, suggest that dopamine release is fast and generates small signaling hotspots. In this review, we summarize progress on the understanding of the dopamine release apparatus and evaluate how its properties may shape dopamine signaling during firing. We discuss how mechanisms of regulation may act through this machinery and propose that striatal architecture for dopamine signaling may have evolved to support rapid dopamine coding.
Topics: Corpus Striatum; Dopamine; Learning; Motivation; Reward
PubMed: 30769276
DOI: 10.1016/j.conb.2019.01.001 -
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 -
Pharmacology, Biochemistry, and Behavior Apr 2014The hypothalamic neuropeptide oxytocin has drawn the attention of scientists for more than a century. The understanding of the function of oxytocin has expanded... (Review)
Review
The hypothalamic neuropeptide oxytocin has drawn the attention of scientists for more than a century. The understanding of the function of oxytocin has expanded dramatically over the years from a simple peptide adept at inducing uterine contractions and milk ejection to a complex neuromodulator with a capacity to shape human social behavior. Decades of research have outlined oxytocin's ability to enhance intricate social activities ranging from pair bonding, sexual activity, affiliative preferences, and parental behaviors. The precise neural mechanisms underlying oxytocin's influence on such behaviors have just begun to be understood. Research suggests that oxytocin interacts closely with the neural pathways responsible for processing motivationally relevant stimuli. In particular, oxytocin appears to impact dopaminergic activity within the mesocorticolimbic dopamine system, which is crucial not only for reward and motivated behavior but also for the expression of affiliative behaviors. Though most of the work performed in this area has been done using animal models, several neuroimaging studies suggest similar relationships may be observed in humans. In order to introduce this topic further, this paper will review the recent evidence that oxytocin may exert some of its social-behavioral effects through its impact on motivational networks.
Topics: Animals; Behavior, Animal; Dopamine; Motivation; Oxytocin; Social Behavior
PubMed: 23850525
DOI: 10.1016/j.pbb.2013.06.011 -
Molecules (Basel, Switzerland) Dec 2017: Parkinson's disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement... (Review)
Review
: Parkinson's disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement therapy, mainly through actual dopamine and its original prodrug l-dopa (LD), faces many challenges such as poor blood brain barrier penetration and decreased response to therapy with time. : The prodrugs described herein are ester, amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, chemical delivery systems and enzyme-models prodrugs designed and made by chemical means, and their bioavailability was studied in animals. A promising ester prodrug for intranasal delivery has been developed. LD methyl ester is currently in Phase III clinical trials. A series of amide prodrugs were synthesized with better stability than ester prodrugs. Both amide and dimeric amide prodrugs offer enhanced blood brain barrier (BBB) penetration and better pharmacokinetics. Attaching LD to sugars has been used to exploit glucose transport mechanisms into the brain. : Till now, no DA prodrug has reached the pharmaceutical market, nevertheless, the future of utilizing prodrugs for the treatment of PD seems to be bright. For instance, LD ester prodrugs have demonstrated an adequate intranasal delivery of LD, thus enabling the absorption of therapeutic agents to the brain. Most of the amide, cyclic, peptidyl or chemical delivery systems of DA prodrugs demonstrated enhanced pharmacokinetic properties.
Topics: Animals; Dopamine; Drug Carriers; Humans; Levodopa; Parkinson Disease; Prodrugs
PubMed: 29295587
DOI: 10.3390/molecules23010040 -
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 -
Brain and Language Aug 2021Dopamine, the main catecholamine neurotransmitter in the brain, is predominately produced in the basal ganglia and released to various brain regions including the...
Dopamine, the main catecholamine neurotransmitter in the brain, is predominately produced in the basal ganglia and released to various brain regions including the frontal cortex, midbrain and brainstem. Dopamine's effects are widespread and include modulation of a number of voluntary and innate behaviors. Vigilant regulation and modulation of dopamine levels throughout the brain is imperative for proper execution of motor behaviors, in particular speech and other types of vocalizations. While dopamine's role in motor circuitry is widely accepted, its unique function in normal and abnormal speech production is not fully understood. In this perspective, we first review the role of dopaminergic circuits in vocal production. We then discuss and propose the conceivable involvement of astrocytes, the numerous star-shaped glia cells of the brain, in the dopaminergic network modulating normal and abnormal vocal productions.
Topics: Astrocytes; Basal Ganglia; Brain; Dopamine; Humans; Speech
PubMed: 34098250
DOI: 10.1016/j.bandl.2021.104970 -
Journal of Neurochemistry Jun 2021The actions of dopamine are essential to relapse to drug seeking but we still lack a precise understanding of how dopamine achieves these effects. Here we review recent... (Review)
Review
The actions of dopamine are essential to relapse to drug seeking but we still lack a precise understanding of how dopamine achieves these effects. Here we review recent advances from animal models in understanding how dopamine controls relapse to drug seeking. These advances have been enabled by important developments in understanding the basic neurochemical, molecular, anatomical, physiological and functional properties of the major dopamine pathways in the mammalian brain. The literature shows that although different forms of relapse to seeking different drugs of abuse each depend on dopamine, there are distinct dopamine mechanisms for relapse. Different circuit-level mechanisms, different populations of dopamine neurons and different activity profiles within these dopamine neurons, are important for driving different forms of relapse. This diversity highlights the need to better understand when, where and how dopamine contributes to relapse behaviours.
Topics: Animals; Dopamine; Drug-Seeking Behavior; Humans; Nucleus Accumbens; Recurrence; Reward; Substance-Related Disorders; Ventral Tegmental Area
PubMed: 33486769
DOI: 10.1111/jnc.15309 -
Current Opinion in Neurobiology Apr 2018Phasic dopamine responses are thought to encode a prediction-error signal consistent with model-free reinforcement learning theories. However, a number of recent... (Review)
Review
Phasic dopamine responses are thought to encode a prediction-error signal consistent with model-free reinforcement learning theories. However, a number of recent findings highlight the influence of model-based computations on dopamine responses, and suggest that dopamine prediction errors reflect more dimensions of an expected outcome than scalar reward value. Here, we review a selection of these recent results and discuss the implications and complications of model-based predictions for computational theories of dopamine and learning.
Topics: Animals; Computer Simulation; Dopamine; Humans; Learning; Models, Neurological; Reinforcement, Psychology
PubMed: 29096115
DOI: 10.1016/j.conb.2017.10.006 -
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