NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory

An Integrative Theory of Prefrontal Cortex Function

2001 • 11,688 citations

A Neural Substrate of Prediction and Reward

1997 • 8,991 citations

The neural basis of drug craving: An incentive-sensitization theory of addiction

1993 • 7,074 citations

Predictive Reward Signal of Dopamine Neurons

1998 • 4,446 citations

What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?

1998 • 3,973 citations

LTP and LTD

2004 • 3,754 citations

Neural systems of reinforcement for drug addiction: from actions to habits to compulsion

2005 • 3,624 citations

Reinforcement Learning

1998 • 3,070 citations

A psychomotor stimulant theory of addiction.

1987 • 2,704 citations

Synaptic Plasticity and Memory: An Evaluation of the Hypothesis

2000 • 2,700 citations

Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

2002 • 2,569 citations

AMPA Receptor Trafficking and Synaptic Plasticity

2002 • 2,540 citations

Drug Dependence, a Chronic Medical Illness

2000 • 2,396 citations

Cellular and Molecular Mechanisms of Drug Dependence

1988 • 2,094 citations

The human orbitofrontal cortex: linking reward to hedonic experience

2005 • 2,077 citations

Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity

1991 • 2,025 citations

10. Reinforcement learning

2020 • 2,008 citations

A framework for mesencephalic dopamine systems based on predictive Hebbian learning

1996 • 2,003 citations

The Structure of Genetic and Environmental Risk Factors for Common Psychiatric and Substance Use Disorders in Men and Women

2003 • 1,859 citations

Molecular basis of long-term plasticity underlying addiction

2001 • 1,831 citations

Learning and Memory Functions of the Basal Ganglia

2002 • 1,698 citations

Parsing reward

2003 • 1,661 citations

Behavioral Theories and the Neurophysiology of Reward

2005 • 1,605 citations

Opioids excite dopamine neurons by hyperpolarization of local interneurons

1992 • 1,585 citations

Limbic Activation During Cue-Induced Cocaine Craving

1999 • 1,518 citations

A cognitive model of drug urges and drug-use behavior: Role of automatic and nonautomatic processes.

1990 • 1,464 citations

Addiction

2002 • 1,444 citations

The Neuroscience of Natural Rewards: Relevance to Addictive Drugs

2002 • 1,439 citations

Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies

2000 • 1,334 citations

Molecular and Cellular Basis of Addiction

1997 • 1,324 citations

Addiction and the brain: The neurobiology of compulsion and its persistence

2001 • 1,284 citations

The many faces of CREB

2005 • 1,282 citations

Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task

1993 • 1,279 citations

Midbrain Dopamine Neurons Encode a Quantitative Reward Prediction Error Signal

2005 • 1,279 citations

The functions of the orbitofrontal cortex

2004 • 1,254 citations

Addiction, a Disease of Compulsion and Drive: Involvement of the Orbitofrontal Cortex

2000 • 1,224 citations

Addiction, Dopamine, and the Molecular Mechanisms of Memory

2000 • 1,186 citations

Encoding Predictive Reward Value in Human Amygdala and Orbitofrontal Cortex

2003 • 1,153 citations

Drugs of Abuse and Stress Trigger a Common Synaptic Adaptation in Dopamine Neurons

2003 • 1,133 citations

Dopamine neurons report an error in the temporal prediction of reward during learning

1998 • 1,115 citations

Controlling the double helix

2003 • 1,102 citations

Evidence for Addiction-like Behavior in the Rat

2004 • 1,089 citations

Structural plasticity associated with exposure to drugs of abuse

2004 • 1,088 citations

Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons

2001 • 1,084 citations

The genetics of addictions: uncovering the genes

2005 • 1,060 citations

The Basal Ganglia and Chunking of Action Repertoires

1998 • 983 citations

Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues

2005 • 977 citations

Computational roles for dopamine in behavioural control

2004 • 957 citations

The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants

1998 • 936 citations

Addiction: A Disease of Learning and Memory

2005 • 920 citations

The principles of learning and behavior

1982 • 910 citations

Decreased dopamine D₂ receptor availability is associated with reduced frontal metabolism in cocaine abusers

1993 • 906 citations

Prefrontal Glutamate Release into the Core of the Nucleus Accumbens Mediates Cocaine-Induced Reinstatement of Drug-Seeking Behavior

2003 • 869 citations

Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the "shell" as compared with the "core" of the rat nucleus accumbens.

1995 • 857 citations

The other side of the engram: experience-driven changes in neuronal intrinsic excitability

2003 • 830 citations

The neuropsychological basis of addictive behaviour

2001 • 796 citations

Nicotine activates and desensitizes midbrain dopamine neurons

1997 • 762 citations

Regulation of Cocaine Reward by CREB

1998 • 762 citations

Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum

2005 • 761 citations

Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse

2003 • 726 citations

Drug Seeking Becomes Compulsive After Prolonged Cocaine Self-Administration

2004 • 721 citations

Cortical rewiring and information storage

2004 • 717 citations

Long-Term Potentiation of Excitatory Inputs to Brain Reward Areas by Nicotine

2000 • 715 citations

Defining the CREB Regulon

2004 • 708 citations

Stress-induced relapse to heroin and cocaine seeking in rats: a review

2000 • 695 citations

Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization

2004 • 685 citations

Conditioning factors in drug abuse: can they explain compulsion?

1998 • 680 citations

Drug-activation of brain reward pathways

1998 • 679 citations

The role of stress in drug self-administration

1998 • 670 citations

Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance.

1975 • 663 citations

Opioid Receptors

2004 • 650 citations

Unmanageable Motivation in Addiction: A Pathology in Prefrontal-Accumbens Glutamate Transmission

2005 • 644 citations

Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats

1984 • 644 citations

Psychomotor stimulant addiction: a neural systems perspective.

2002 • 635 citations

Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine

1999 • 630 citations

Regulation of gene expression and cocaine reward by CREB and ΔFosB

2003 • 623 citations

Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine

2001 • 622 citations

Mechanisms of Amphetamine Action Revealed in Mice Lacking the Dopamine Transporter

1998 • 622 citations

Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens

2002 • 609 citations

Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories

2005 • 592 citations

Psychomotor Stimulant Addiction: A Neural Systems Perspective

2002 • 573 citations

Cingulate Hypoactivity in Cocaine Users During a GO-NOGO Task as Revealed by Event-Related Functional Magnetic Resonance Imaging

2003 • 551 citations

Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments

1994 • 549 citations

Reinforcement Learning

1997 • 548 citations

Neural Activity Related to Drug Craving in Cocaine Addiction

2001 • 545 citations

Neuronal Activity Related to Reward Value and Motivation in Primate Frontal Cortex

2004 • 539 citations

Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs

2003 • 516 citations

CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli

2002 • 506 citations

Addiction as a Computational Process Gone Awry

2004 • 505 citations

Illicit Psychoactive Substance Use, Heavy Use, Abuse, and Dependence in a US Population-Based Sample of Male Twins

2000 • 502 citations

Neural Systems and Cue-Induced Cocaine Craving,

2002 • 497 citations

Extrathalamic Modulation of Cortical Function

1987 • 480 citations

Differential control over cocaine-seeking behavior by nucleus accumbens core and shell

2004 • 478 citations

Regulation of immediate early gene expression and AP-1 binding in the rat nucleus accumbens by chronic cocaine.

1992 • 466 citations

Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats

1991 • 441 citations

Benzodiazepine use, abuse, and dependence.

2005 • 437 citations

Incubation of cocaine craving after withdrawal: a review of preclinical data

2004 • 425 citations

Interaction between glucocorticoid hormones, stress and psychostimulant drugs*

2002 • 415 citations

Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition

2003 • 410 citations

CREB and the formation of long-term memory

1996 • 399 citations

Orbitofrontal Cortex, Associative Learning, and Expectancies

2005 • 397 citations

ΔFosB: a molecular switch for long-term adaptation in the brain

2004 • 395 citations

Computational perspectives on dopamine function in prefrontal cortex

2002 • 387 citations

Involvement of the Dorsal Striatum in Cue-Controlled Cocaine Seeking

2005 • 386 citations

Neuronal Correlates of Goal-Based Motor Selection in the Prefrontal Cortex

2003 • 385 citations

Appetitive behavior: impact of amygdala-dependent mechanisms of emotional learning.

2003 • 384 citations

Neuropharmacological Mechanisms of Drug Reward: Beyond Dopamine in the Nucleus Accumbens

1998 • 382 citations

Limbic-Striatal Memory Systems and Drug Addiction

2002 • 381 citations

D1/D5 Dopamine Receptor Activation Increases the Magnitude of Early Long-Term Potentiation at CA1 Hippocampal Synapses

1996 • 374 citations

Identification of PSD-95 as a Regulator of Dopamine-Mediated Synaptic and Behavioral Plasticity

2004 • 372 citations

Neural Activation Patterns of Methamphetamine-Dependent Subjects During Decision Making Predict Relapse

2005 • 372 citations

Essential Role of D1 But Not D2 Receptors in the NMDA Receptor-Dependent Long-Term Potentiation at Hippocampal-Prefrontal Cortex SynapsesIn Vivo

2000 • 369 citations

Neuronal adaptation to amphetamine and dopamine: Molecular mechanisms of prodynorphin gene regulation in rat striatum

1995 • 364 citations

Common Molecular and Cellular Substrates of Addiction and Memory

2002 • 361 citations

Amphetamine regulates gene expression in rat striatum via transcription factor CREB

1994 • 356 citations

Glutamate systems in cocaine addiction

2003 • 349 citations

Drug Dependence, a Chronic Medical Illness: Implications for Treatment, Insurance, and Outcomes Evaluation

2001 • 348 citations

Molecular Neurobiology of Drug Addiction

2004 • 347 citations

A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug use

1998 • 346 citations

CREB modulates excitability of nucleus accumbens neurons

2006 • 340 citations

Dopamine Modulation of State-Dependent Endocannabinoid Release and Long-Term Depression in the Striatum

2005 • 339 citations

A Complex Program of Striatal Gene Expression Induced by Dopaminergic Stimulation

1998 • 333 citations

Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking behaviour

2003 • 317 citations

Properties and Plasticity of Excitatory Synapses on Dopaminergic and GABAergic Cells in the Ventral Tegmental Area

1999 • 317 citations

Corticotropin-Releasing Factor Requires CRF Binding Protein to Potentiate NMDA Receptors via CRF Receptor 2 in Dopamine Neurons

2003 • 297 citations

Appetitive Behavior

2003 • 295 citations

Reduction of Morphine Abstinence in Mice with a Mutation in the Gene Encoding CREB

1996 • 293 citations

Nicotinic excitation of rat ventral tegmental neurones in vitro studied by intracellular recording

1989 • 291 citations

Acute and Chronic Cocaine-Induced Potentiation of Synaptic Strength in the Ventral Tegmental Area: Electrophysiological and Behavioral Correlates in Individual Rats

2004 • 290 citations

Amphetamine and Dopamine-Induced Immediate Early Gene Expression in Striatal Neurons Depends on Postsynaptic NMDA Receptors and Calcium

1996 • 287 citations

Nucleus Accumbens Long-Term Depression and the Expression of Behavioral Sensitization

2005 • 286 citations

Fos B mutant mice: Loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine’s psychomotor and rewarding effects

1997 • 283 citations

Elevated levels of GluR1 in the midbrain: a trigger for sensitization to drugs of abuse?

2002 • 279 citations

Sensitization to Morphine Induced by Viral-Mediated Gene Transfer

1997 • 279 citations

Sensitization to the psychomotor stimulant effects of amphetamine: Modulation by associative learning.

1996 • 275 citations

Morphine reward in dopamine-deficient mice

2005 • 273 citations

Classical conditioning of a morphine abstinence phenomenon, reinforcement of opioid-drinking behavior and ?relapse? in morphine-addicted rats

1967 • 273 citations

Reward without Dopamine

2003 • 269 citations

An essential role for ΔFosB in the nucleus accumbens in morphine action

2006 • 264 citations

Effects of lesions of prefrontal cortex, amygdala, or fornix on behavioral sensitization to amphetamine: Comparison with N-methyl-d-aspartate antagonists

1995 • 263 citations

Genetic approaches to memory storage

1999 • 262 citations

Enhanced Vulnerability to Cocaine Self-Administration Is Associated with Elevated Impulse Activity of Midbrain Dopamine Neurons

2000 • 256 citations

Distinguishing Whether Dopamine Regulates Liking, Wanting, and/or Learning About Rewards.

2005 • 243 citations

Quaternary Structure, Protein Dynamics, and Synaptic Function of SAP97 Controlled by L27 Domain Interactions

2004 • 243 citations

Hippocampal Long-Term Potentiation Is Reduced by Chronic Opiate Treatment and Can Be Restored by Re-Exposure to Opiates

2002 • 241 citations

Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5

2003 • 237 citations

Activator of G Protein Signaling 3

2004 • 231 citations

Learning Mechanisms in Addiction: Synaptic Plasticity in the Ventral Tegmental Area as a Result of Exposure to Drugs of Abuse

2004 • 230 citations

Homer Proteins Regulate Sensitivity to Cocaine

2004 • 226 citations

A Common Mechanism Mediates Long-Term Changes in Synaptic Transmission after Chronic Cocaine and Morphine

1996 • 224 citations

Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors

2004 • 224 citations

Generation of Silent Synapses by Acute In Vivo Expression of CaMKIV and CREB

2005 • 218 citations

Is craving the source of compulsive drug use?

1998 • 216 citations

Striatal Cell Type-Specific Overexpression of ΔFosB Enhances Incentive for Cocaine

2003 • 216 citations

Modulation of Long-Term Depression by Dopamine in the Mesolimbic System

2000 • 211 citations

A single in-vivo exposure to Δ9THC blocks endocannabinoid-mediated synaptic plasticity

2004 • 211 citations

Whole-Cell Plasticity in Cocaine Withdrawal: Reduced Sodium Currents in Nucleus Accumbens Neurons

1998 • 209 citations

μ-Opioid Receptor and CREB Activation Are Required for Nicotine Reward

2005 • 208 citations

Regional and Cellular Mapping of cAMP Response Element-Mediated Transcription during Naltrexone-Precipitated Morphine Withdrawal

2002 • 207 citations

Influence of novel versus home environments on sensitization to the psychomotor stimulant effects of cocaine and amphetamine

1995 • 207 citations

Simultaneous LTP of non-NMDA- and LTD of NMDA-receptor-mediated responses in the nucleus accumbens

1994 • 205 citations

Dopamine facilitates long-term depression of glutamatergic transmission in rat prefrontal cortex

1998 • 201 citations

A SingleIn VivoExposure to Cocaine Abolishes Endocannabinoid-Mediated Long-Term Depression in the Nucleus Accumbens

2004 • 201 citations

Sensitization to the behavioral effects of cocaine: Modification by Pavlovian conditioning

1981 • 197 citations

Integrity of the mesocortical dopaminergic system is necessary for complete expression of in vivo hippocampal–prefrontal cortex long-term potentiation

1999 • 190 citations

Functional Tolerance and Blockade of Long-Term Depression at Synapses in the Nucleus Accumbens after Chronic Cannabinoid Exposure

2003 • 187 citations

Regulation of drug-taking and -seeking behaviors by neuroadaptations in the mesolimbic dopamine system

2004 • 185 citations

Different Requirements for cAMP Response Element Binding Protein in Positive and Negative Reinforcing Properties of Drugs of Abuse

2001 • 178 citations

In vivo nicotine treatment regulates mesocorticolimbic CREB and ERK signaling in C57Bl/6J mice

2003 • 176 citations

Amphetamine Modulates Human Incentive Processing

2004 • 171 citations

Regulation of Drug Reward by cAMP Response Element-Binding Protein: Evidence for Two Functionally Distinct Subregions of the Ventral Tegmental Area

2005 • 166 citations

Critical Role for Ventral Tegmental Glutamate in Preference for a Cocaine-Conditioned Environment

2003 • 162 citations

Cocaine-induced potentiation of synaptic strength in dopamine neurons: Behavioral correlates in GluRA(–/–) mice

2004 • 160 citations

d-Amphetamine-induced behavioral sensitization: implication of a glutamatergic medial prefrontal cortex–ventral tegmental area innervation

1999 • 156 citations

Sensitization occurs to the locomotor effects of morphine and the specific μ opioid receptor agonist, DAGO, administered repeatedly to the ventral tegmental area but not to the nucleus accumbens

1987 • 152 citations

Amphetamine Blocks Long-Term Synaptic Depression in the Ventral Tegmental Area

2000 • 151 citations

Where is the locus in opioid withdrawal?

1997 • 143 citations

Reinstatement of heroin self-administration habits: morphine prompts and naltrexone discourages renewed responding after extinction

1992 • 141 citations

A psychomotor stimulant theory of addiction.

1987 • 141 citations

Self-administration enhances excitatory synaptic transmission in the bed nucleus of the stria terminalis

2005 • 137 citations

Inducible repression of CREB function disrupts amygdala-dependent memory

2004 • 137 citations

Functional heterogeneity of the rat medial prefrontal cortex: effects of discrete subarea‐specific lesions on drug‐induced conditioned place preference and behavioural sensitization

1999 • 131 citations

Cocaine-Induced Plasticity of Intrinsic Membrane Properties in Prefrontal Cortex Pyramidal Neurons: Adaptations in Potassium Currents

2005 • 125 citations

Acute and chronic cocaine administration differentially alters striatal opioid and nuclear transcription factor mRNAs

1994 • 124 citations

Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons

2001 • 122 citations

The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction

2004 • 110 citations

Inducible, brain region-specific expression of a dominant negative mutant of c-Jun in transgenic mice decreases sensitivity to cocaine

2003 • 105 citations

Long-Term Potentiation in the Rat Hippocampus Is Reversibly Depressed by Chronic Intermittent Ethanol Exposure

2002 • 104 citations

Repeated Cocaine Administration Increases Voltage-Sensitive Calcium Currents in Response to Membrane Depolarization in Medial Prefrontal Cortex Pyramidal Neurons

2005 • 104 citations

Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration

2004 • 102 citations

The Endogenous Cannabinoid Anandamide and Its Synthetic Analog R(+)-Methanandamide Are Intravenously Self-Administered by Squirrel Monkeys

2005 • 101 citations

Enhanced Inhibition of Synaptic Transmission by Dopamine in the Nucleus Accumbens during Behavioral Sensitization to Cocaine

2002 • 101 citations

Repeated Cocaine Treatment Decreases Whole-Cell Calcium Current in Rat Nucleus Accumbens Neurons

2002 • 100 citations

Differential distribution of CREB in the mesolimbic dopamine reward pathway

2003 • 99 citations

Dopamine and Glutamate Induce Distinct Striatal Splice Forms of Ania-6, an RNA Polymerase II-Associated Cyclin

2001 • 94 citations

Regulation of CRE‐mediated transcription in mouse brain by amphetamine

2003 • 92 citations

Inhibition by MK-801 of cocaine-induced sensitization, conditioned place preference, and dopamine-receptor supersensitivity in mice

1996 • 85 citations

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

2005 • 84 citations

Enhancement of long-term potentiation in the rat hippocampus following cocaine exposure

2002 • 80 citations

Repeated Cocaine Administration Suppresses HVA-Ca²⁺Potentials and Enhances Activity of K⁺Channels in Rat Nucleus Accumbens Neurons

2004 • 78 citations

Opioid tolerance and dependence — do they matter?

2004 • 74 citations

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

2004 • 74 citations

Chronic d-amphetamine in nucleus accumbens: Lack of tolerance or reverse tolerance of locomotor activity

1981 • 72 citations

Sensitization to cocaine's motor activating properties produced by electrical kindling of the medial prefrontal cortex but not of the hippocampus

1994 • 70 citations

Repeated exposure to amphetamine disrupts dopaminergic modulation of excitatory synaptic plasticity and neurotransmission in nucleus accumbens

2003 • 69 citations

Decreased Presynaptic Sensitivity to Adenosine after Cocaine Withdrawal

1998 • 68 citations

Cocaine-induced modulation of long-term potentiation in the CA1 region of rat hippocampus

2005 • 62 citations

Amphetamine-induced conditioned activity and sensitization: the role of habituation to the test context and the involvement of Pavlovian processes

1998 • 57 citations

Selective Inhibition by Adenosine of mGluR IPSPs in Dopamine Neurons After Cocaine Treatment

2000 • 41 citations

Hippocampal Long-Term Potentiation Is Reduced by Chronic Opiate Treatment and Can Be Restored by Re-Exposure to Opiates

2005 • 26 citations

Cocaine-seeking behavior after extended cocaine-free periods in rats: role of conditioned stimuli

2002 • 21 citations

Opposite Effects of GluR1 and PKA‐Resistant GluR1 Overexpression in the Ventral Tegmental Area on Cocaine Reinforcement

2003 • 8 citations