Neurocircuitry of Addiction

Description

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. 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 A B C D E F G H I J K L M N O P Q R S T V W Back Cover