People use drugs for many different reasons, including the pursuit of "high," social factors and self-medication of other conditions. Many millions of people are addicted to at least one substance, and the cost of addiction is immense, at both the individual and societal levels. Neurocircuitry of Addiction is the first book of its kind, with a focus on addiction neuroscience from a neural circuit perspective. This book begins with a primer on circuit-based neuroscience that equips the reader with an understanding of the applications described throughout the book. Each subsequent chapter positions a different brain region at the "center" of addiction neurocircuitry and goes on to describe the anatomical connectivity of that brain region, how those circuits are affected by drug exposure, and the role of those circuits in controlling addiction-related behaviors. All chapters of this book are written by content experts for a target audience that has some basic neuroscience background, but no prior in-depth knowledge regarding the neurocircuitry of addiction.
Author(s): Nicholas W. Gilpin
Publisher: Academic Press
Year: 2022
Language: English
Pages: 557
City: London
Front Cover
NEUROCIRCUITRY OF ADDICTION
NEUROCIRCUITRY OF ADDICTION
Copyright
Contents
Contributors
Preface
1 - Leveraging circuits to understand addiction
Introduction
Identification of neural circuits implicated in addiction: where to start?
Human histopathological techniques
Application of molecular biology techniques to human samples
Neuroimaging techniques in clinical studies
Preclinical research methods to identify circuits and their adaptations to addictive drugs
Neural tracing techniques
Conventional tracers
Characterization of circuits through cell type identification
Genetic approaches to identifying circuits
Genetic targeting approaches
Viral vector approaches to dissecting neural circuits
Identifying neuroadaptations in neural circuits
Electrophysiology techniques
In vivo techniques for measuring cellular activity
Interrogating neural circuit function in vivo
Conclusions
References
2 - Midbrain (VTA) circuits
VTA heterogenous neuronal composition
VTA neuronal activity is regulated by converging inputs from multiple brain areas
Plastic changes associated with drug intake in midbrain dopamine circuits
VTA DA neurons and pathways involved in the reinforcing effects of drugs of abuse
VTA DA neurons and withdrawal
Transition to compulsion in addiction
Drug addiction and long-term memory
VTA dopamine neurons and relapse to seeking drugs of abuse
VTA DA neurons and their outputs in reinstatement to drug seeking
Inputs to VTA DA neurons and reinstatement to drug seeking
Acknowledgments
References
3 - Striatal circuits
Introduction
Anatomy of the striatum
The striatum: cells and circuits
The striatum in action selection
The nucleus accumbens: motivated behavior and addiction
The dorsal striatum: motivated behavior and addiction
Stress, habits, and addiction
Striatal circuits in motivated behavior and addiction
Orbitofrontal cortex→dorsal striatum
Medial prefrontal cortex→nucleus accumbens/dorsomedial striatum
Hippocampus→nucleus accumbens
Somatosensory and motor cortex→dorsolateral striatum
Thalamus→nucleus accumbens/dorsal striatum
Amygdala→nucleus accumbens/dorsal striatum
Inhibitory striatal circuits in motivated behavior and addiction
Sex differences in substance use disorder
Conclusions
Bibliography
4 - Prefrontal Cortical (PFC) circuits
Introduction
Functional neuroanatomy of the PFC
Human anatomy
Rodent PFC
PFC dysfunction and addiction
Drug self-administration and seeking
Inhibitory control
Attentional bias
Decision making
Summary
Structure and physiology of the PFC
Principal pyramidal neurons
Interneurons
Drug-induced adaptations
Effects on pyramidal neuron activity
Alterations in ionic conductance in mPFC neurons
Excitatory and inhibitory plasticity
PFC circuit-specific plasticity
Relevance of drug-induced changes in mPFC plasticity
Impact of biological sex, stress, and preexisting differences on addiction and PFC function
Sex differences in prevalence, progression, and neural mechanisms
Impact of stress
Pre-existing differences
Conclusions
References
5 - Insular Cortical circuits
Insula neuroanatomy and structure
Functions of the insula
Interoception
Self-recognition
Body awareness
Emotions
Taste
Olfaction
Viscero-sensation
Visceromotor control
Somatosensory functions
Auditory functions
Vestibular functions
Pain
Temperature perception
Somatomotor control
Speech
Cognition
Empathy and compassion
Decision making and gambling
Addiction
Evidence implicating the insula in addiction
Nicotine
Alcohol
Cocaine
Amphetamine
Opioids
Cannabis
Conclusions
References
6 - Thalamic circuits
Overview of the thalamus
The thalamus and substance use disorder: overview
The thalamus: human studies
The thalamus and cocaine misuse in humans
The thalamus and opioid abuse in humans
The thalamus and alcohol use disorder in humans
The thalamus and polysubstance use disorder
The thalamus: preclinical studies
The paraventricular nucleus of the thalamus: preclinical studies
Hypothalamic → PVT circuitry: preclinical studies
Paraventricular nucleus of the thalamus → nucleus accumbens circuitry: preclinical studies
Other PVT circuits in drug addiction: preclinical studies
Other thalamic nuclei
Mediodorsal nucleus of the thalamus and drug addiction: preclinical studies
Lateral habenula and drug addiction: preclinical studies
Medial habenula and drug addiction: preclinical studies
Conclusions
Acknowledgments
References
7 - Hippocampal circuits
Introduction
Hippocampal formation
Synaptic plasticity in the hippocampus
Intra-hippocampal circuitry
Hippocampal circuit connections with other brain regions
Dentate gyrus
CA1, CA2 and CA3
Synaptic plasticity in hippocampal sub-regions
CA1
CA3
Dentate gyrus
Neurogenesis as a form of plasticity in the DG
Adult neurogenesis in the DG influences synaptic plasticity in the DG
Regulation of plasticity in the hippocampus by addictive drugs
Cocaine
Cocaine and hippocampal plasticity
Cocaine reward and reinforcement
Cocaine and hippocampus-dependent behaviors
Alcohol
Alcohol and hippocampal plasticity
Alcohol reward and reinforcement
Alcohol and hippocampus-dependent behaviors
Conclusions
Acknowledgments
References
8 - Amygdala circuits
Introduction
Local circuit between the basolateral and central amygdala
Basolateral amygdala circuitry
Projections from BLA to NAc in addiction
Projections from BLA to DMS in addiction
Reciprocal circuits between BLA and PFC in addiction
Reciprocal circuits between BLA and HPC in addiction
Projections from BLA to BNST in addiction
Reciprocal circuits between BLA and IC in addiction
Reciprocal circuits between BLA and TH in addiction
Projections from VTA to BLA in addiction
Projections from LC to BLA in addiction
Projections from the NBM to BLA in addiction
Central amygdala circuits
Reciprocal circuits between CeA and PBN in addiction
Reciprocal circuits between CeA and PVT in addiction
Reciprocal circuits between CeA and HPT in addiction
Reciprocal circuits between CeA and RN in addiction
Reciprocal circuits between CeA and VTA/SN in addiction
Circuitry from IC to CeA in addiction
Reciprocal circuits between CeA and LC in addiction
Circuitry from CeA to BNST in addiction
Reciprocal circuits between CeA and PAG in addiction
Reciprocal circuits between CeA and NTS in addiction
Conclusions
Funding sources
References
9 - Bed Nucleus of Stria Terminalis (BNST) circuits
Introduction
BNST subregions and cell types
Anatomical subregions of the BNST
Anterior BNST
Posterior BNST
Anatomy of the human BNST
BNST cell type heterogeneity
BNST afferents and efferents
Glutamate/GABA
Glutamate pharmacology
Glutamatergic afferents
GABA pharmacology
GABAergic afferents
Neuromodulators
Neuropeptide pharmacology
Neuropeptide afferents
Monoamines
Dopamine pharmacology
Dopaminergic afferents
Noradrenaline pharmacology
Noradrenergic afferents
Serotonin pharmacology
Serotonergic afferents
Endogenous cannabinoids
Endocannabinoid modulation of BNST afferents
BNST efferents
Effects of acute and chronic drug exposure on the BNST
Alcohol
Opioids
Cocaine
Amphetamines
Nicotine
Cannabinoids
Long term effects of drugs of abuse on the BNST
Early withdrawal
Protracted abstinence
Relapse
Chemogenetic and optogenetic circuit manipulation in the BNST
Translational work in the human BNST
Future of BNST circuitry and addiction
References
10 - Noradrenergic circuits
Norepinephrine synthesis, storage, receptors, transporters, and metabolism
Anatomy/development of norepinephrine circuits
Norepinephrine involvement in stress, arousal, and locomotion
Neurochemical techniques used for measuring brain NE cell and circuit activity
Manipulating/probing NE circuits
Norepinephrine and opioids
Manipulating NE levels
Manipulating post-synaptic receptors
Regulation of NE physiology and release by opioid system
Norepinephrine and alcohol
Manipulating NE levels
Manipulating post-synaptic receptors
Norepinephrine and psychostimulants
Manipulating NE levels
Manipulating post-synaptic receptors
Norepinephrine and other substances of abuse
Nicotine
Cannabinoids
Norepinephrine, natural rewards/psychosocial reward
Feeding behavior
Exercise
Gambling behavior
Social behavior
Conclusions
References
11 - Cholinergic modulation of circuits
The discovery of acetylcholine
From nodes to circuits
Acetylcholine anatomy and circuitry
Acetylcholine mediated behaviors
Reward-related signaling: mesopontine tegmentum to VTA circuit
Role of VTA acetylcholine in drug reward
VTA mAChRs in drug reward
VTA nAChRs in drug reward
Functional differences between VTA nAChR and mAChR
Cholinergic circuits in the NAc
Tonically active cholinergic interneurons in the NAc
Comparison of cholinergic input to the VTA and NAc
Role of acetylcholine in the basolateral amygdala
Role of acetylcholine in the prefrontal cortex
Aversion-related signaling: habenula to interpeduncular circuit
Medial habenulo-interpeduncular (MHb-IPN) circuit
MHb-IPN nicotine-mediated behaviors
Lateral habenula (LHb)
Septal circuits
Septo-hippocampal circuit
Septo-habenula circuit
Cerebellum
Conclusions
References
12 - Gut-brain axis
Introduction
The gut-brain axis
Gastrointestinal neuroendocrine pathways
Ghrelin
Ghrelin and alcohol
Preclinical studies
Human studies
Ghrelin and cannabinoids
Preclinical studies
Human studies
Ghrelin and nicotine
Preclinical studies
Human studies
Ghrelin and opioids
Preclinical studies
Ghrelin and stimulants
Preclinical studies
Human studies
GLP-1
GLP-1 and alcohol
Preclinical studies
Human studies
GLP-1 and cannabinoids
Preclinical studies
Human studies
GLP-1 and nicotine
Human studies
GLP-1 and opioids
Preclinical studies
GLP-1 and stimulants
Preclinical studies
Human studies
Microbiome
Drug-induced changes in diversity and taxonomic structure of the microbiome and in metabolism (resulting metabolites)
Short-chain fatty acids
Bile acids
Tryptophan metabolites
Microbial diversity
Alcohol
Cannabinoids
Nicotine
Opioids
Psychostimulants
Conclusions
Funding and disclosure
References
13 - Circadian circuits
Introduction
Circadian rhythms
Functional and anatomical organization of the circadian system
Circadian rhythms in brain and periphery: role of the molecular clock
Molecular clocks, reward, and substance use
Associations between circadian genes and substance use and dependence
Substance use alters circadian genes in the brain
Connections between molecular clocks, energetics, and neural circuits involved in reward
Circadian modulation of neural circuitry involved in substance reward
The conductor of circadian rhythms: role of the suprachiasmatic nucleus (SCN) in the synchronization and coordination of ci ...
SCN neural circuit efferents
SCN neural circuit afferents
Midbrain dopaminergic inputs to the SCN
Raphe serotonergic inputs to the SCN
Environmental circadian perturbations and substance use
Changes in photoperiod, light–dark schedules, and light at night
Circadian “misalignment” and substance use vulnerability: a focus on adolescents
Chronotype impacts reward neural circuit functions
Loss of rhythms and loss of control
Conclusions
References
Index
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K
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M
N
O
P
Q
R
S
T
V
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