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Neuroscience and Biobehavioral Reviews Apr 2010Schizophrenia is a chronic, severe, and disabling brain disorder arising from the adverse interaction of predisposing risk genes and environmental factors. The... (Review)
Review
Schizophrenia is a chronic, severe, and disabling brain disorder arising from the adverse interaction of predisposing risk genes and environmental factors. The psychopathology is characterized by a wide array of disturbing cognitive, emotional, and behavioral symptoms that interfere with the individual's capacity to function in society. Contemporary pathophysiological models assume that psychotic symptoms are triggered by a dysregulation of dopaminergic activity in the brain, a theory that is tightly linked to the serendipitous discovery of the first effective antipsychotic agents in the early 1950s. In recent years, the availability of modern neuroimaging techniques has significantly expanded our understanding of the key mediator circuits that bridge the gap between genetic susceptibility and clinical phenotype. This paper discusses the pathophysiological concepts, molecular mechanisms and neuroimaging evidence that link psychosis to disturbances in dopamine neurotransmission.
Topics: Animals; Brain; Dopamine; Humans; Mental Disorders; Models, Neurological; Phenotype
PubMed: 19559045
DOI: 10.1016/j.neubiorev.2009.06.005 -
Proceedings of the National Academy of... Mar 2023Dopamine (DA) loss in Parkinson's disease (PD) causes debilitating motor deficits. However, dopamine is also widely linked to reward prediction and learning, and the...
Dopamine (DA) loss in Parkinson's disease (PD) causes debilitating motor deficits. However, dopamine is also widely linked to reward prediction and learning, and the contribution of dopamine-dependent learning to movements that are impaired in PD-which often do not lead to explicit rewards-is unclear. Here, we used two distinct motor tasks to dissociate dopamine's acute motoric effects vs. its long-lasting, learning-mediated effects. In dopamine-depleted mice, motor task performance gradually worsened with task exposure. Task experience was critical, as mice that remained in the home cage during the same period were relatively unimpaired when subsequently probed on the task. Repeated dopamine replacement treatments acutely rescued deficits and gradually induced long-term rescue that persisted despite treatment withdrawal. Surprisingly, both long-term rescue and parkinsonian performance decline were task specific, implicating dopamine-dependent learning. D1R activation potently induced acute rescue that gradually consolidated into long-term rescue. Conversely, reduced D2R activation potently induced parkinsonian decline. In dopamine-depleted mice, either D1R activation or D2R activation prevented parkinsonian decline, and both restored balanced activation of direct vs. indirect striatal pathways. These findings suggest that reinforcement and maintenance of movements-even movements not leading to explicit rewards-are fundamental functions of dopamine and provide potential mechanisms for the hitherto unexplained "long-duration response" by dopaminergic therapies in PD.
Topics: Mice; Animals; Dopamine; Neurons; Corpus Striatum; Learning; Parkinson Disease
PubMed: 36920928
DOI: 10.1073/pnas.2213093120 -
International Journal of Environmental... Sep 2022Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined...
Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined associations between the work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic nervous system activity, indicative of stress. We recruited participants (n = 219; 2018-2019) from a cardiovascular risk cohort to investigate workplace culture, well-being, and stress. Participants completed seven questionnaires. Urine samples were used to measure catecholamines and their metabolites by LC/MS/MS. Pearson correlation and linear regression models were used after adjusting for demographics and creatinine. Participants reporting higher well-being had lower urinary levels of dopamine, serotonin, and 3-methoxytyramine. Participants reporting a more engaged and more positive workplace had lower levels of dopamine and 3-methoxytyramine. Reported workplace isolation was correlated with higher levels of dopamine and 3-methoxytyramine. Given correlations between catecholamines, we used 3-methoxytyramine for linear regression. In fully adjusted models, in environments with a more positive culture, levels of 3-methoxytyramine remained lower (β = -0.065 ± 0.025, = 0.01) and indicated a positive association between workplace isolation and 3-methoxytyramine (β = 0.064 ± 0.030, = 0.04). These findings are consistent with an important relationship between workplace environment and sympathetic nervous system activity.
Topics: Biomarkers; Catecholamines; Creatinine; Dopamine; Humans; Serotonin; Tandem Mass Spectrometry; Workplace
PubMed: 36231223
DOI: 10.3390/ijerph191911920 -
Neurosciences (Riyadh, Saudi Arabia) Jan 2023Parkinson's disease (PD) is a progressive widespread neurodegenerative disorder affecting the brain. It is characterized by dopaminergic neuron degeneration in the... (Review)
Review
Parkinson's disease (PD) is a progressive widespread neurodegenerative disorder affecting the brain. It is characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta (SNpc). Current therapeutic options ease the symptoms of PD; however, they have multiple undesirable effects and do not slow the disease progression. Exercise by itself has many positive impacts on general health. In this review, the positive impact of different forms of exercise were found to improve motor and non-motor symptoms in PD. Exercise effects is mediate by multiple mechanisms, including the upregulation of brain-derived neurotrophic factor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, and autophagy regulating proteins; and downregulates proinflammatory cytokines. In this review, the significance of exercise in PD, as well as in the prevention and maintenance of the disease was discussed. Many questions are left unanswered in this manuscript, including potential genetic factors underlying response to exercise. Therefore, further high-quality studies on humans are needed.
Topics: Humans; Animals; Parkinson Disease; Dopamine; Exercise; Dopaminergic Neurons; Disease Models, Animal
PubMed: 36617448
DOI: 10.17712/nsj.2023.1.20220105 -
Neuropharmacology Oct 2007Dopamine has undergone extensive investigation due to its known involvement in a number of neurological and psychiatric disorders. In particular, studies into... (Review)
Review
Dopamine has undergone extensive investigation due to its known involvement in a number of neurological and psychiatric disorders. In particular, studies into pathological conditions have focused on the roles of high amplitude, phasically evoked dopamine release in regions such as the prefrontal cortex and striatum. However, research has shown that dopamine release can be more complex than just phasic release; thus, there is also a tonic, background dopamine release, with alterations in tonic dopamine release likely having unique and important functional roles. Unfortunately, however, tonic dopamine release has received relatively little attention. In this review, we summarize our recent studies and discuss how modulation of the dopamine system, both in terms of phasic activation and attenuation of tonic dopamine are important for the functions of brain regions receiving this dopamine innervation, and that imbalances in these dopamine release mechanisms may play a significant role in psychiatric disorders such as schizophrenia.
Topics: Animals; Dopamine; Electrophysiology; Humans; Mental Disorders; Neuronal Plasticity; Neurons, Afferent; Nucleus Accumbens; Stress, Psychological
PubMed: 17709119
DOI: 10.1016/j.neuropharm.2007.07.007 -
Current Opinion in Neurobiology Apr 2017Dopamine is associated with a variety of conserved responses across species including locomotion, sleep, food consumption, aggression, courtship, addiction and several... (Review)
Review
Dopamine is associated with a variety of conserved responses across species including locomotion, sleep, food consumption, aggression, courtship, addiction and several forms of appetitive and aversive memory. Historically, dopamine has been most prominently associated with dynamics underlying reward, punishment, or salience. Recent emerging evidence from Drosophila supports a role in all of these functions, as well as additional roles in the interplay between external sensation and internal states and forgetting of the very memories dopamine helped encode. We discuss how cell-specific resolution and manipulation are elucidating the rules of dopamine's involvement in encoding valence and memory.
Topics: Animals; Dopamine; Drosophila; Memory; Punishment; Reward
PubMed: 28088703
DOI: 10.1016/j.conb.2016.12.011 -
Neuron Oct 2002Recent neurophysiological studies reveal that neurons in certain brain structures carry specific signals about past and future rewards. Dopamine neurons display a... (Review)
Review
Recent neurophysiological studies reveal that neurons in certain brain structures carry specific signals about past and future rewards. Dopamine neurons display a short-latency, phasic reward signal indicating the difference between actual and predicted rewards. The signal is useful for enhancing neuronal processing and learning behavioral reactions. It is distinctly different from dopamine's tonic enabling of numerous behavioral processes. Neurons in the striatum, frontal cortex, and amygdala also process reward information but provide more differentiated information for identifying and anticipating rewards and organizing goal-directed behavior. The different reward signals have complementary functions, and the optimal use of rewards in voluntary behavior would benefit from interactions between the signals. Addictive psychostimulant drugs may exert their action by amplifying the dopamine reward signal.
Topics: Animals; Brain; Dopamine; Humans; Illicit Drugs; Neurons; Reward
PubMed: 12383780
DOI: 10.1016/s0896-6273(02)00967-4 -
Neuroscience Dec 2014Dopamine D2-autoreceptors play a key role in regulating the activity of dopamine neurons and control the synthesis, release and uptake of dopamine. These Gi/o-coupled... (Review)
Review
Dopamine D2-autoreceptors play a key role in regulating the activity of dopamine neurons and control the synthesis, release and uptake of dopamine. These Gi/o-coupled inhibitory receptors play a major part in shaping dopamine transmission. Found at both somatodendritic and axonal sites, autoreceptors regulate the firing patterns of dopamine neurons and control the timing and amount of dopamine released from their terminals in target regions. Alterations in the expression and activity of autoreceptors are thought to contribute to Parkinson's disease as well as schizophrenia, drug addiction and attention-deficit hyperactivity disorder (ADHD), which emphasizes the importance of D2-autoreceptors in regulating the dopamine system. This review will summarize the cellular actions of dopamine autoreceptors and discuss recent advances that have furthered our understanding of the mechanisms by which D2-receptors control dopamine transmission.
Topics: Animals; Autoreceptors; Dopamine; Dopaminergic Neurons; Receptors, Dopamine D2; Reward
PubMed: 24463000
DOI: 10.1016/j.neuroscience.2014.01.025 -
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 -
Cell Reports Oct 2022Goal-directed navigation requires learning to accurately estimate location and select optimal actions in each location. Midbrain dopamine neurons are involved in reward...
Goal-directed navigation requires learning to accurately estimate location and select optimal actions in each location. Midbrain dopamine neurons are involved in reward value learning and have been linked to reward location learning. They are therefore ideally placed to provide teaching signals for goal-directed navigation. By imaging dopamine neural activity as mice learned to actively navigate a closed-loop virtual reality corridor to obtain reward, we observe phasic and pre-reward ramping dopamine activity, which are modulated by learning stage and task engagement. A Q-learning model incorporating position inference recapitulates our results, displaying prediction errors resembling phasic and ramping dopamine neural activity. The model predicts that ramping is followed by improved task performance, which we confirm in our experimental data, indicating that the dopamine ramp may have a teaching effect. Our results suggest that midbrain dopamine neurons encode phasic and ramping reward prediction error signals to improve goal-directed navigation.
Topics: Animals; Dopamine; Dopaminergic Neurons; Goals; Mesencephalon; Mice; Reward
PubMed: 36223748
DOI: 10.1016/j.celrep.2022.111470