A Neural Circuit Mechanism for Encoding Aversive Stimuli in the Mesolimbic Dopamine System

Neuron, Год журнала: 2018, Номер 101(1), С. 133 - 151.e7

Опубликована: Ноя. 29, 2018

Язык: Английский

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Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties

Nature Neuroscience, Год журнала: 2018, Номер 21(8), С. 1072 - 1083

Опубликована: Июль 19, 2018

Язык: Английский

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Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine

JAMA Psychiatry, Год журнала: 2017, Номер 74(5), С. 511 - 511

Опубликована: Март 15, 2017

Stimulant use disorder is common, affecting between 0.3% and 1.1% of the population, costs more than $85 billion per year globally. There are no licensed treatments to date. Several lines evidence implicate dopamine system in pathogenesis substance disorder. Therefore, understanding nature dysfunction seen stimulant users has potential aid development new therapeutics.To comprehensively review vivo imaging for dopaminergic alterations (cocaine, amphetamine, or methamphetamine) abuse dependence.The entire PubMed, EMBASE, PsycINFO databases were searched studies from inception date May 14, 2016.Case-control identified that compared measures healthy controls using positron emission tomography single-photon computed measure striatal synthesis release assess transporter availability receptor availability.Demographic, clinical, extracted each study, meta-analyses sensitivity analyses conducted stimulants combined, as well cocaine amphetamine methamphetamine separately if there sufficient studies.Differences measured (assessed change D2/D3 after administration methylphenidate), availability, users, controls.A total 31 519 512 included final analysis. In most studies, duration abstinence varied 5 days 3 weeks. was a significant decrease with controls: effect size -0.84 (95% CI, -1.08 -0.60; P < .001) combined -0.87 -1.15 cocaine. addition, availability: -0.91 -1.50 -0.32; .01) -1.47 -1.83 -1.10; methamphetamine. also -0.76 -0.92 -0.73 -0.94 -0.53; cocaine, -0.81 -1.12 -0.49; Consistent not found vesicular monoamine transporter, synthesis, D1 studies.Data suggest both presynaptic postsynaptic aspects striatum down-regulated users. The commonality differences these findings discrepancies preclinical literature models drug addiction discussed, their implications future development.

Язык: Английский

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The Molecular Basis of Drug Addiction: Linking Epigenetic to Synaptic and Circuit Mechanisms

Neuron, Год журнала: 2019, Номер 102(1), С. 48 - 59

Опубликована: Апрель 1, 2019

Язык: Английский

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Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising Therapeutic Targets in Psychiatric Illness

Frontiers in Systems Neuroscience, Год журнала: 2017, Номер 11

Опубликована: Апрель 27, 2017

Corticostriatal circuits through the orbitofrontal cortex (OFC) play key roles in complex human behaviours such as evaluation, affect regulation, and reward-based decision-making. Importantly, medial lateral OFC have functionally anatomically distinct connectivity profiles which differentially contribute to various aspects of goal-directed behaviour. corticostriatal been consistently implicated across a wide range psychiatric disorders, including major depressive disorder (MDD), obsessive compulsive (OCD), substance use disorders (SUDs). Furthermore, related dysfunction can be addressed via conventional novel neurostimulatory techniques, deep brain stimulation (DBS), electroconvulsive therapy (ECT), repetitive transcranial (rTMS), direct current (tDCS). Such techniques elicit changes activity, resulting clinical symptomatology. Here we review available literature regarding how disturbances functioning lead symptomatology aforementioned treatments may exert their therapeutic effect by rectifying abnormal activity. First, role reward-guided learning, decision-making, regulation reappraisal. Second, discuss circuit disorders. Third, evidence that mechanisms neuromodulation directly involve activity circuits. Finally, examine potential future applications targeted at circuitry; specifically, growing field individually-tailored therapies personalized medicine psychiatry.

Язык: Английский

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The Emergence of a Circuit Model for Addiction

Annual Review of Neuroscience, Год журнала: 2016, Номер 39(1), С. 257 - 276

Опубликована: Май 5, 2016

Addiction is a disease of altered behavior. Addicts use drugs compulsively and will continue to do so despite negative consequences. Even after prolonged periods abstinence, addicts are at risk relapse, particularly when cues evoke memories that associated with drug use. Rodent models mimic many the core components addiction, from initial reinforcement cue-associated relapse continued intake have also enabled unprecedented mechanistic insight into revealing plasticity glutamatergic synaptic transmission evoked by strong activation mesolimbic dopamine—a defining feature all addictive drugs—as neural substrate for these drug-adaptive behaviors. Cell type–specific optogenetic manipulations allowed both identification relevant circuits design protocols reverse drug-evoked establish links causality The emergence circuit model addiction open door novel therapies, such as deep brain stimulation.

Язык: Английский

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Distributed and Mixed Information in Monosynaptic Inputs to Dopamine Neurons

Neuron, Год журнала: 2016, Номер 91(6), С. 1374 - 1389

Опубликована: Сен. 1, 2016

Язык: Английский

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Reward and Aversion

Annual Review of Neuroscience, Год журнала: 2016, Номер 39(1), С. 297 - 324

Опубликована: Май 5, 2016

To benefit from opportunities and cope with challenges in the environment, animals must adapt their behavior to acquire rewards avoid punishments. Maladaptive changes neuromodulatory systems neural circuits for reward aversion can lead manifestation of several prominent psychiatric disorders including addiction depression. Recent progress is pushing boundaries knowledge on two major fronts research aversion: First, new layers complexity have been reported functions dopamine (DA) serotonin (5-HT) aversion. Second, specific circuit components pathways that encode begun be identified. This review aims outline historic perspectives insights into DA 5-HT coding distinct rewards. It also highlights recent advances studies enabled by technologies, such as cell-type-specific electrophysiology tracing, optogenetics-based behavioral manipulation. may provide guidance developing novel treatment strategies neuropsychiatric diseases related malfunction system.

Язык: Английский

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Linking RDoC and HiTOP: A new interface for advancing psychiatric nosology and neuroscience

Clinical Psychology Review, Год журнала: 2021, Номер 86, С. 102025 - 102025

Опубликована: Март 24, 2021

Язык: Английский

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Circuit Mechanisms of Reward, Anhedonia, and Depression

The International Journal of Neuropsychopharmacology, Год журнала: 2018, Номер 22(2), С. 105 - 118

Опубликована: Сен. 12, 2018

Pleasure and motivation are important factors for goal-directed behavior well-being in both animals humans. Intact hedonic capacity requires an undisturbed interplay between a number of different brain regions transmitter systems. Concordantly, dysfunction networks encoding reward have been shown depression other psychiatric disorders. The development technological possibilities to investigate connectivity on functional level humans directly influence using optogenetics among techniques has provided new insights this field research.In review, we aim provide overview the neurobiological substrates anhedonia network level. For purpose, definition involved components described first, then current data healthy individuals depressed patients summarized, roles neurotransmitter systems processing specified. Based information, impact therapeutic approaches is with particular focus deep stimulation (DBS) as possibility direct modulation human structures vivo.Overall, results studies emphasize importance disorders relevance targeting phenotype successful treatment. However, more incorporating these refinement methodological needed be able develop individually tailored concepts based clinical profiles patients.

Язык: Английский

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