Neuroimaging Impaired Response Inhibition and Salience Attribution in Human Drug Addiction: A Systematic Review

Neuron, Journal Year: 2018, Volume and Issue: 98(5), P. 886 - 903

Published: June 1, 2018

Language: Английский

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Volitional social interaction prevents drug addiction in rat models

Nature Neuroscience, Journal Year: 2018, Volume and Issue: 21(11), P. 1520 - 1529

Published: Oct. 11, 2018

Language: Английский

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Simple Behavioral Analysis (SimBA) – an open source toolkit for computer classification of complex social behaviors in experimental animals

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: April 20, 2020

Abstract Aberrant social behavior is a core feature of many neuropsychiatric disorders, yet the study complex in freely moving rodents relatively infrequently incorporated into preclinical models. This likely contributes to limited translational impact. A major bottleneck for adoption socially complex, ethology-rich, procedures are technical limitations consistently annotating detailed behavioral repertoires rodent behavior. Manual annotation subjective, prone observer drift, and extremely time-intensive. Commercial approaches expensive inferior manual annotation. Open-source alternatives often require significant investments specialized hardware computational programming knowledge. By combining recent advances convolutional neural networks pose-estimation with further machine learning analysis, primed inclusion under umbrella neuroethology. Here we present an open-source package graphical interface workflow (Simple Behavioral Analysis, SimBA) that uses create supervised predictive classifiers behavior, millisecond resolution accuracies can out-perform human observers. SimBA does not video acquisition nor extensive background. Standard descriptive statistical along region interest annotation, provided addition classifier generation. To increase ease-of-use behavioural neuroscientists, designed accessible menus pre-processing videos, training datasets, selecting advanced options, robust validation functions flexible visualizations tools. allows transparency, explainability tunability prior to, during, experimental use. We demonstrate this approach both mice rats by classifying behaviors commonly central brain function motivation. Finally, provide library poseestimation weights resident-intruder rats. All code data, together tutorials documentation, available on GitHub repository . Graphical abstract (GUI) creating (a) Pre-process videos supports common (e.g., cropping, clipping, sampling, format conversion, etc.) be performed either single or as batch. (b) Managing data classification projects Pose-estimation tracking DeepLabCut DeepPoseKit imported created managed within user interface, results projects. also userdrawn region-of-interests (ROIs) statistics animal movements, features (c) Create classifiers, perform classifications, analyze has tools correcting inaccuracies when multiple subjects frame, events from optimizing hyperparameters discrimination thresholds. number checkpoints logs included increased Both summary at end analysis. accepts annotations generated elsewhere (such through JWatcher) (d) Visualize several options visualizing movements ROI analyzing durations frequencies classified behaviors. See comprehensive documentation tutorials.

Language: Английский

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A molecular mechanism for choosing alcohol over an alternative reward

Science, Journal Year: 2018, Volume and Issue: 360(6395), P. 1321 - 1326

Published: June 21, 2018

Alcohol addiction leads to increased choice of alcohol over healthy rewards. We established an exclusive procedure in which ~15% outbred rats chose a high-value reward. These animals displayed addiction-like traits, including high motivation obtain and pursuit this drug despite adverse consequences. Expression the γ-aminobutyric acid (GABA) transporter GAT-3 was selectively decreased within amygdala alcohol-choosing rats, whereas knockdown transcript reversed preference that originally sweet solution alcohol. expression central alcohol-dependent people compared those who died unrelated causes. Impaired GABA clearance contributes addiction, appears translate between species, may offer targets for new pharmacotherapies treating disorder.

Language: Английский

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Addiction as a brain disease revised: why it still matters, and the need for consilience

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 46(10), P. 1715 - 1723

Published: Feb. 22, 2021

The view that substance addiction is a brain disease, although widely accepted in the neuroscience community, has become subject to acerbic criticism recent years. These criticisms state disease deterministic, fails account for heterogeneity remission and recovery, places too much emphasis on compulsive dimension of addiction, specific neural signature not been identified. We acknowledge some these have merit, but assert foundational premise neurobiological basis fundamentally sound. also emphasize denying harmful standpoint since it contributes reducing access healthcare treatment, consequences which are catastrophic. Here, we therefore address criticisms, doing so provide contemporary update addiction. arguments support this view, discuss why apparently spontaneous does negate it, how seemingly behaviors can co-exist with sensitivity alternative reinforcement Most importantly, argue biological substrate from both capacity behavior change arise, arguing an intensified neuroscientific study recovery. More broadly, propose disagreements reveal need multidisciplinary research integrates neuroscientific, behavioral, clinical, sociocultural perspectives.

Language: Английский

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Improving translation of animal models of addiction and relapse by reverse translation

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(11), P. 625 - 643

Published: Oct. 6, 2020

Language: Английский

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Social vulnerabilities for substance use: Stressors, socially toxic environments, and discrimination and racism

Neuropharmacology, Journal Year: 2021, Volume and Issue: 188, P. 108518 - 108518

Published: March 12, 2021

Applying a social determinants of health framework, this review brings attention to evidence from sciences and neuroscience on the role selected factors in individual population-level vulnerability substance use disorders (SUDs). The understanding that SUDs is multifaceted occurs across different levels influence (individual, interpersonal, community, societal) underscored. We propose socially based stressors play critical creating SUDs, as such, deserve greater empirical further understand how they "get under skin." Current knowledge relationships among resulting stressors, exposure toxic childhood environments, racism discrimination are summarized discussed, implications for future research, practice, policy. Specifically, we using top-down approach examination known, yet often unexplored, between related inequities, potential differential effects demographic groups. Finally, research gaps promising areas policy focused ameliorating vulnerabilities associated with lifespan presented. This article part special issue 'Vulnerabilities Substance Abuse'.

Language: Английский

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Understanding Addiction Using Animal Models

Frontiers in Behavioral Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: Nov. 29, 2019

Drug addiction is a neuropsychiatric disorder with grave personal consequences that has extraordinary global economic impact. Despite decades of research, the options available to treat are often ineffective because our rudimentary understanding drug-induced pathology in brain circuits and synaptic physiology inhibits rational design successful therapies. This will arise first from animal models were experimentation at level molecular biology possible. We review most common preclinical addictive behavior, discuss advantages disadvantages each. includes non-contingent which animals passively exposed rewarding substances, as well widely used contingent such drug self-administration relapse. For latter, we elaborate on different ways mimicking craving relapse, include using acute stress, administration or exposure cues previously paired self-administration. further describe paradigms where taking challenged by alternative rewards, appetitive foods social interaction. In an attempt better model individual vulnerability abuse characterizes human addiction, field also established behaviors ranked various criteria use presence negative consequences. Separation more vulnerable according these criteria, along other innate predispositions including goal- sign-tracking, sensation-seeking behavior impulsivity, genetic susceptibilities develop relapse vulnerability. examine current behavioral addictions gambling, included DSM-5, exercise, mentioned DSM-5 but not yet due insufficient peer-reviewed evidence. Finally, after reviewing face validity aforementioned models, consider standardized tests pharmaceutical companies assess potential during clinical trials.

Language: Английский

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Sex Differences in Opioid and Psychostimulant Craving and Relapse: A Critical Review

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 74(1), P. 119 - 140

Published: Jan. 1, 2022

A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences psychostimulant opioid Next, reinstatement of seeking after extinction self-administration, incubation (time-dependent increase during abstinence). We also discuss ovarian hormones' role relapse humans animal models speculate brain mechanisms underlying their cocaine rodent models. Finally, imaging responses cues stress men women.The results reviewed do not appear support notion women However, this conclusion tentative because most were correlational, sufficiently powered, a priori designed detect differences. Additionally, suggest stress. The provide evidence for stress-induced but cue- or cocaine-induced seeking. These modulated part by hormones. In contrast, available data relapse/reinstatement methamphetamine opioids

Significance Statement

This systematic summarizes Results

Language: Английский

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Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and vivo single-neuron calcium imaging, we found that drugs augment dopaminoceptive ensemble activity nucleus accumbens (NAc) disorganize overlapping responses natural rewards a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, single-nucleus RNA sequencing, identified Rheb as molecular substrate regulates signal transduction NAc while enabling suppress consumption. Mapping NAc-projecting regions activated revealed input-specific effects on These findings characterize dynamic, circuit basis common pathway, wherein interfere with fulfillment innate needs.

Language: Английский

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