Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development

Pharmacological Reviews, Journal Year: 2020, Volume and Issue: 73(1), P. 163 - 201

Published: Dec. 14, 2020

Compulsive drug seeking that is associated with addiction hypothesized to follow a heuristic framework involves three stages (binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation) domains of dysfunction (incentive salience/pathologic habits, negative emotional states, executive function, respectively) via changes in the basal ganglia, extended amygdala/habenula, frontal cortex, respectively. This review focuses on neurochemical/neurocircuitry dysregulations contribute hyperkatifeia, defined as greater intensity emotional/motivational signs symptoms during withdrawal from drugs abuse affect stage cycle. Hyperkatifeia provides an additional source motivation for compulsive reinforcement. Negative reinforcement reflects increase probability response remove aversive stimulus or hyperkatifeia augmented by genetic/epigenetic vulnerability, environmental trauma, psychiatric comorbidity. Neurobiological targets involve neurocircuitry amygdala its connections within-system neuroadaptations dopamine, enkephalin/endorphin opioid peptide, γ-aminobutyric acid/glutamate systems between-system prostress corticotropin-releasing factor, norepinephrine, glucocorticoid, dynorphin, hypocretin, neuroimmune antistress neuropeptide Y, nociceptin, endocannabinoid, oxytocin systems. Such are mediate hedonic set point gradually gains allostatic load shifts homeostatic state state. Based preclinical studies translational date, medications behavioral therapies reset brain stress, antistress, pain return them homeostasis would be promising new medication development.

Significance Statement

The focus this cycle driving force addiction. Medications reverse resetting returning

Language: Английский

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Role of the bed nucleus of the stria terminalis in aversive learning and memory

Learning & Memory, Journal Year: 2017, Volume and Issue: 24(9), P. 480 - 491

Published: Aug. 16, 2017

Surviving threats in the environment requires brain circuits for detecting (or anticipating) danger and coordinating appropriate defensive responses (e.g., increased cardiac output, stress hormone release, freezing behavior). The bed nucleus of stria terminalis (BNST) is a critical interface between "affective forebrain"-including amygdala, ventral hippocampus, medial prefrontal cortex-and hypothalamic brainstem areas that have been implicated neuroendocrine, autonomic, behavioral to actual or anticipated threats. However, precise contribution BNST behavior unclear, both terms antecedent stimuli mobilize activity consequent reactions. For example, it well known essential contextual fear conditioning, but dispensable conditioning discrete conditioned (CSs), at least as indexed by behavior. recent evidence suggests there are circumstances which may persist independent BNST. Furthermore, involved reinstatement relapse) extinguished CSs. As such, gaps understanding how contributes fundamental processes Pavlovian conditioning. Here, we attempt provide an integrative account function We discuss distinctions unconditioned role organizing behaviors associated with these states. propose mediates responses-not based on modality duration threat response threat-but rather consequence ability stimulus predict when aversive outcome will occur (i.e., its temporal predictability). argue not uniquely mobilized sustained responses. In contrast, poorly

Language: Английский

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The Raphe Dopamine System Controls the Expression of Incentive Memory

Neuron, Journal Year: 2020, Volume and Issue: 106(3), P. 498 - 514.e8

Published: March 6, 2020

Language: Английский

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The paraventricular thalamus provides a polysynaptic brake on limbic CRF neurons to sex-dependently blunt binge alcohol drinking and avoidance behavior in mice

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Aug. 23, 2021

Abstract Bed nucleus of the stria terminalis (BNST) neurons that synthesize corticotropin-releasing factor (CRF) drive binge alcohol drinking and anxiety. Here, we found female C57BL/6J mice drink more than males have greater basal BNST CRF neuron excitability synaptic excitation. We identified a dense VGLUT2 + input from paraventricular thalamus (PVT) releases glutamate directly onto but also engages large interneuron population to ultimately inhibit neurons, this polysynaptic PVT -BNST circuit is robust in females males. Chemogenetic inhibition projection promoted only mice, while activation reduced avoidance behavior both sexes. Lastly, repeated produced female-like phenotype male PVT-BNST excitatory synapse without altering function per se. Our data describe complex, feedforward inhibitory sex-dependent its function, behavioral roles, alcohol-induced plasticity.

Language: Английский

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Vagal Interoceptive Modulation of Motivated Behavior

Physiology, Journal Year: 2018, Volume and Issue: 33(2), P. 151 - 167

Published: Feb. 7, 2018

In addition to regulating the ingestion and digestion of food, sensory feedback from gut brain modifies emotional state motivated behavior by subconsciously shaping cognitive affective responses events that bias behavioral choice. This focused review highlights evidence gut-derived signals impact engaging vagal afferents central neural circuits generally serve limit or terminate goal-directed approach behaviors, initiate maintain avoidance.

Language: Английский

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The paraventricular thalamic nucleus: A key hub of neural circuits underlying drug addiction

Pharmacological Research, Journal Year: 2019, Volume and Issue: 142, P. 70 - 76

Published: Feb. 14, 2019

Language: Английский

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Distinct Transcriptomic Cell Types and Neural Circuits of the Subiculum and Prosubiculum along the Dorsal-Ventral Axis

Cell Reports, Journal Year: 2020, Volume and Issue: 31(7), P. 107648 - 107648

Published: May 1, 2020

Subicular regions play important roles in spatial processing and many cognitive functions, these are mainly attributed to the subiculum (Sub) rather than prosubiculum (PS). Using single-cell RNA sequencing, we identify 27 transcriptomic cell types residing sub-domains of Sub PS. Based on situ expression reliable markers, precise boundaries PS consistently defined along dorsoventral axis. borders evaluate Cre-line specificity tracer injections, find bona fide projections topographically structures for navigation. In contrast, sends its outputs widespread brain crucial motivation, emotion, reward, stress, anxiety, fear. The PS, respectively, dominate dorsal ventral subicular receive different afferents. These results reveal two molecularly anatomically distinct circuits centered providing a consistent explanation historical data clearer foundation future studies.

Language: Английский

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Cues conditioned to withdrawal and negative reinforcement: Neglected but key motivational elements driving opioid addiction

Science Advances, Journal Year: 2021, Volume and Issue: 7(15)

Published: April 7, 2021

Cues associated with negative reinforcement can stimulate relapse and contribute to opioid use disorder.

Language: Английский

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Noradrenergic circuits and signaling in substance use disorders

Neuropharmacology, Journal Year: 2022, Volume and Issue: 208, P. 108997 - 108997

Published: Feb. 14, 2022

Language: Английский

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Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder

Current topics in behavioral neurosciences, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Language: Английский

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