Neurobiological substrates for the dark side of compulsivity in addiction.

paper Cited Public

Authors: Koob, George F
Year: 2009
Journal: Neuropharmacology
PMID: 18725236
DOI: 10.1016/j.neuropharm.2008.07.043
PMCID: PMC2637927

Drug addiction can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreases in dopamine and opioid peptide function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, increases in anxiety-like responses, and increases in extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of addiction. Other components of brain stress systems in the extended amygdala that interact with CRF and may contribute to the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least in part, the compulsivity of addiction.

#	Section	Preview
40	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	Administration of CRF1 antagonists systemically reversed the increased self-administration of…
41	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	As noted above, CRF in parts of the extended amygdala is involved in the aversive stimulus effects…
42	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	Also, as noted above, precipitated withdrawal from chronic nicotine produced anxiogenic-like effects…
43	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	A particularly dramatic example of the motivational effects of CRF in dependence can be observed in…
44	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	post-acute withdrawal) (O’Dell et al., 2004; Rimondini et al., 2002). Intracerebroventricular…
45	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	Although less well developed, evidence exists for a role of norepinephrine systems in the extended…
46	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	et al., 2008b). A focal point for many of these effects is the extended amygdala but at the level of…
47	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	The dynamic nature of the brain stress system response to challenge is illustrated by the pronounced…
48	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	Neuropeptide Y (NPY) is a neuropeptide with dramatic anxiolytic-like properties localized to the…
49	3. Neural Substrates for Increased Drug-taking with Extended Access — 3.2. Between-system neuroadaptations	Thus, acute withdrawal from drugs increases CRF in the central nucleus of the amygdala that has…
50	4. Compulsivity in addiction: An allostatic view	Compulsivity in addiction can derive from multiple sources, including enhanced incentive salience,…
51	4. Compulsivity in addiction: An allostatic view	to form the neurobiological basis for the b-process: loss of function in the reward systems…
52	4. Compulsivity in addiction: An allostatic view	An overall conceptual theme argued here is that drug addiction represents a break with homeostatic…
53	4. Compulsivity in addiction: An allostatic view	Allostasis, originally conceptualized to explain persistent morbidity of arousal and autonomic…
54	4. Compulsivity in addiction: An allostatic view	Allostatic mechanisms have been hypothesized to be involved in maintaining a functioning brain…
55	4. Compulsivity in addiction: An allostatic view	Repeated challenges, such as with drugs of abuse, lead to attempts of the brain via molecular,…

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In this knowledge base

Title	Year	PMID
Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability.	2018	28439100
Subjective response to alcohol among alcohol-dependent individuals: effects of the μ-opioid receptor (OPRM1) gene and alcoholism severity.	2013	23240711
Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems.	2011	21530666
Muscarinic type 2 receptors in the lateral dorsal tegmental area modulate cocaine and food seeking behavior in rats.	2010	20667466

External

Title	Authors	Journal	Year	Link
Pathology of oral nicotine pouches and their addiction mechanisms.	Zou H et al.	—	2026	→
Traumatic-like fear memory recall causes persistent morphine conditioned place preference in drug withdrawn male mice.	Leconte C et al.	—	2026	→
5-HT 2A receptor inverse agonist attenuates morphine withdrawal syndrome and its aversiveness in rats.	Tsai PH et al.	—	2025	→
A review of kappa opioid receptor antagonists and their clinical trial landscape.	Lobe MMM et al.	—	2025	→
Binge-type eating disorders and ultra-processed food addiction: phenomenology, pathophysiology and treatment implications.	Ifland J et al.	—	2025	→
Calcium imaging of central amygdala activity after escalation of fentanyl self-administration.	Malone SG et al.	—	2025	→
Development and validation of the Compulsive Substance Use Questionnaire: Attending to substance use automaticity, craving, and continued use despite negative consequences.	Taghian NR et al.	—	2025	→
Dihydrotestosterone regulation of stress-related behaviors in mice exposed to subchronic variable stress.	Rybka KA et al.	—	2025	→
Effects of suvorexant on diurnal cortisol and patient-reported stress during opioid withdrawal in a randomized trial.	McKendrick G et al.	—	2025	→
From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration.	Basavarajappa BS et al.	—	2025	→
Neurospirituality Connectome - Role in Neurology and Reward Deficiency Syndrome (RDS).	Blum K et al.	—	2025	→
Plasma metabolic profiles in alcohol use disorder: diagnostic role of arginine and emotional implications of N6-acetyl-lysine and succinic acid.	Cao G et al.	—	2025	→
Regulation of Dopamine Transporter Surface Expression.	Besada C et al.	—	2025	→
Withdrawal catastrophizing scale: initial psychometric properties and implications for the study of opioid use disorder and hyperkatifeia.	Hall OT et al.	—	2025	→
Withdrawal interference scale: a novel measure of withdrawal-related life disruption in opioid use disorder and alcohol use disorder.	Hall OT et al.	—	2025	→
Basal cortisol level modulates stress-induced opioid-seeking behavior.	Greenwald MK et al.	—	2024	→
Cognitive impairment as a predictor of long-term psychological distress in patients with polysubstance use disorders: a prospective longitudinal cohort study.	Hetland J et al.	—	2024	→
Cortical paired associative stimulation shows impaired plasticity of inhibition networks as a function of chronic alcohol use.	Sallie SN et al.	—	2024	→
Environmental enrichment enhances ethanol preference over social reward in male swiss mice: Involvement of oxytocin-dopamine interactions.	Rae M et al.	—	2024	→
Multi-modal neuroimaging reveals differences in alcohol-cue reactivity but not neurometabolite concentrations in adolescents who drink alcohol.	Kirkland AE et al.	—	2024	→
Neuropathic pain has sex-specific effects on oxycodone-seeking and non-drug-seeking ensemble neurons in the dorsomedial prefrontal cortex of mice.	Sarka BC et al.	—	2024	→
Sex-specific negative affect-like behaviour and parabrachial nucleus activation induced by BNST stimulation in adult mice with adolescent alcohol history.	Albrechet-Souza L et al.	—	2024	→
The effects of buprenorphine and morphine during pregnancy: Impact of exposure length on maternal brain, behavior, and offspring neurodevelopment.	Myers AM et al.	—	2024	→
The Perceived Role of Withdrawal in Maintaining Opioid Addiction among Adults with Untreated Opioid Use Disorder: A Survey of Syringe Exchange Program Participants.	Hall OT et al.	—	2024	→
Voluntary Exercise Ameliorates Chronic Ethanol Withdrawal-Induced Adaptations of Opioid Receptor Expression in the Nucleus Accumbens, Dopamine Release, and Ethanol Consumption.	Nelson CA et al.	—	2024	→
Blunted Expected Reward Value Signals in Binge Alcohol Drinkers.	Tolomeo S et al.	—	2023	→
Fibromyalgia predicts increased odds of pain-related addiction exacerbation among individuals with pain and opioid use disorder.	Hall OT et al.	—	2023	→
Gender-Specific Interactions in a Visual Object Recognition Task in Persons with Opioid Use Disorder.	Petrie J et al.	—	2023	→
LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal.	Ren Z et al.	—	2023	→
Neuropathic pain has sex-specific effects on oxycodone seeking and drug-seeking ensembles in the dorsomedial prefrontal cortex	Sarka BC et al.	—	2023	—
N-Oleoyl Glycine and Its Derivatives Attenuate the Acquisition and Expression of Cocaine-Induced Behaviors.	Shahen-Zoabi S et al.	—	2023	→
PYY<sub>3-36</sub> infused systemically or directly into the VTA attenuates fentanyl seeking in male rats.	Caffrey A et al.	—	2023	→
The antidepressant agomelatine attenuates morphine-induced reinstatement but not self-administration or precipitated withdrawal.	De A et al.	—	2023	→
The development of compulsive coping behavior depends on dorsolateral striatum dopamine-dependent mechanisms.	Marti-Prats L et al.	—	2023	→
The effect of emotion regulation on emotional eating among undergraduate students in China: The chain mediating role of impulsivity and depressive symptoms.	Yang H et al.	—	2023	→
Alcohol solution strength preference predicts compulsive-like drinking behavior in rats.	Foo JC et al.	—	2022	→
A neuroeconomic signature of opioid craving: How fluctuations in craving bias drug-related and nondrug-related value.	Biernacki K et al.	—	2022	→
An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement.	Tian G et al.	—	2022	→
Central sensitization in opioid use disorder: a novel application of the American College of Rheumatology Fibromyalgia Survey Criteria.	Hall OT et al.	—	2022	→
Comparing associations between mood and breath alcohol concentration in the laboratory and natural environment.	Haney AM et al.	—	2022	→
Delayed crises following benzodiazepine withdrawal: deficient adaptive mechanisms or simple pharmacokinetics? Detoxification assisted by serum-benzodiazepine elimination tracking.	Basińska-Szafrańska A	—	2022	→
Natural Products for the Treatment of Drug Addiction: Narrative Review.	Raslan MA	—	2022	→
Negative symptoms in alcohol use disorder: A pilot study applying the two-factor model of negative symptoms to patients with alcohol use disorder.	Buschner M et al.	—	2022	→
Oxytocin and vasopressin: Signalling, behavioural modulation and potential therapeutic effects.	Rae M et al.	—	2022	→
The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study.	Grundinger N et al.	—	2022	→
Transcranial direct current stimulation (tDCS) reduces motivation to drink ethanol and reacquisition of ethanol self-administration in female mice.	Pedron S et al.	—	2022	→
Utility of 'substance use disorder' as a heuristic for understanding overeating and obesity.	O'Connor RM et al.	—	2022	→
A Brain on Cannabinoids: The Role of Dopamine Release in Reward Seeking and Addiction.	Peters KZ et al.	—	2021	→
Addiction and Sleep Disorders.	Ek J et al.	—	2021	→
Binge ethanol drinking associated with sex-dependent plasticity of neurons in the insula that project to the bed nucleus of the stria terminalis.	Marino RAM et al.	—	2021	→
Caveolin-1 Expression in the Dorsal Striatum Drives Methamphetamine Addiction-Like Behavior.	Avchalumov Y et al.	—	2021	→
Dysregulation of Nociceptin/Orphanin FQ and Dynorphin Systems in the Extended Amygdala of Alcohol Preferring Marchigian Sardinian (msP) Rats.	Caputi FF et al.	—	2021	→
Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes.	Lewicky JD et al.	—	2021	→
Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice.	Calarco CA et al.	—	2021	→
Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective.	Jones JA et al.	—	2021	→
Recent Perceived Stress, Amygdala Reactivity to Acute Psychosocial Stress, and Alcohol and Cannabis Use in Adolescents and Young Adults With Bipolar Disorder.	Le V et al.	—	2021	→
SR-17018 Stimulates Atypical µ-Opioid Receptor Phosphorylation and Dephosphorylation.	Fritzwanker S et al.	—	2021	→
Stress induces reinstatement of extinguished cocaine conditioned place preference by a sequential signaling via neuropeptide S, orexin, and endocannabinoid.	Chou YH et al.	—	2021	→
Study protocol: evaluation of the addictive potential of e-cigarettes (EVAPE): neurobiological, sociological, and epidemiological perspectives.	Vollstädt-Klein S et al.	—	2021	→
The role of withdrawal in mesocorticolimbic drug cue reactivity in opioid use disorder.	Shi Z et al.	—	2021	→
Transcriptional analysis of the response of C. elegans to ethanol exposure.	Sterken MG et al.	—	2021	→
A Light in the Darkness: Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat the Hedonic Dysregulation of Addiction.	Pettorruso M et al.	—	2020	→
Allosteric modulation of metabotropic glutamate receptors in alcohol use disorder: Insights from preclinical investigations.	Johnson KA et al.	—	2020	→
ASF (a Compound of Traditional Chinese Medicine) in the treatment of patients with alcohol dependence: Study protocol of a randomized, double-blinded, placebo-controlled clinical trial.	Liang X et al.	—	2020	→
Cocaine-induced ischemia in prefrontal cortex is associated with escalation of cocaine intake in rodents.	Du C et al.	—	2020	→
HIV Infection and Neurocognitive Disorders in the Context of Chronic Drug Abuse: Evidence for Divergent Findings Dependent upon Prior Drug History.	Illenberger JM et al.	—	2020	→
Increases in compulsivity, inflammation, and neural injury in HIV transgenic rats with escalated methamphetamine self-administration under extended-access conditions.	de Guglielmo G et al.	—	2020	→
Learning to lose control: A process-based account of behavioral addiction.	Perales JC et al.	—	2020	→
Non-pharmacological factors that determine drug use and addiction.	Ahmed SH et al.	—	2020	→
Paternal exposure to morphine during adolescence potentiates morphine withdrawal in male offspring: Involvement of the lateral paragigantocellularis nucleus.	Azadi M et al.	—	2020	→
Potential of the zebrafish model for the forensic toxicology screening of NPS: A comparative study of the effects of APINAC and methiopropamine on the behavior of zebrafish larvae and mice.	Morbiato E et al.	—	2020	→
Repeated restraint stress potentiates methylphenidate and modafinil-induced behavioral sensitization in rats.	Alam N et al.	—	2020	→
Revealing a compulsive phenotype in cholinergic M<sub>4</sub><sup>-/-</sup> mice depends on the inter-trial interval initiation settings in a five choice serial reaction time task.	Justinussen J et al.	—	2020	→
Role for kappa-opioid system in stress-induced cocaine use uncovered with PET.	Blevins D et al.	—	2020	→
Spontaneous Early Withdrawal Behaviors after Chronic 24-hour Free-Choice Access to Ethanol.	Hauser SR et al.	—	2020	→
Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study.	Chye Y et al.	—	2020	→
The recognition and management of protracted alcohol withdrawal may improve and modulate the pharmacological treatment of alcohol use disorder.	Caputo F et al.	—	2020	→
The transition to compulsion in addiction.	Lüscher C et al.	—	2020	→
Alteration to hippocampal volume and shape confined to cannabis dependence: a multi-site study.	Chye Y et al.	—	2019	→
Anti-relapse neurons in the infralimbic cortex of rats drive relapse-suppression by drug omission cues.	Laque A et al.	—	2019	→
A structural MRI study of differential neuromorphometric characteristics of binge and heavy drinking.	Maksimovskiy AL et al.	—	2019	→
Cognitive impairment in substance use disorders.	Ramey T et al.	—	2019	→
Comorbidity of opioid-related and anxiety-related symptoms and disorders.	Langdon KJ et al.	—	2019	→
Correlates and Potential Confounds of Cannabis Withdrawal Among High-Risk Adolescents.	Ellingson JM et al.	—	2019	→
Defining Compulsive Behavior.	Luigjes J et al.	—	2019	→
Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin/hypocretin-1 receptor antagonist in rats.	James MH et al.	—	2019	→
Kappa-opioid receptors, dynorphin, and cocaine addiction: a positron emission tomography study.	Martinez D et al.	—	2019	→
Morphine-dependent and abstinent mice are characterized by a broader distribution of the neurons co-expressing mu and delta opioid receptors.	Pierre F et al.	—	2019	→
MP1104, a mixed kappa-delta opioid receptor agonist has anti-cocaine properties with reduced side-effects in rats.	Atigari DV et al.	—	2019	→
Naltrexone effects on subjective responses to alcohol in the human laboratory: A systematic review and meta-analysis.	Ray LA et al.	—	2019	→
Neuroimaging of reward mechanisms in Gambling disorder: an integrative review.	Clark L et al.	—	2019	→
Smoking relapse risk is increased among individuals in recovery.	Quisenberry AJ et al.	—	2019	→
Systemic oxytocin administration alters mesolimbic dopamine release in mice.	Estes MK et al.	—	2019	→
The effects of acute stress on consummatory and motivational responses for sucrose in rats after long-term withdrawal from morphine.	Bai Y et al.	—	2019	→
The impact of sugar consumption on stress driven, emotional and addictive behaviors.	Jacques A et al.	—	2019	→
Amino acid modulation of dopamine in the nucleus accumbens mediates sex differences in nicotine withdrawal.	Carcoba LM et al.	—	2018	→
Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival.	Guevara A et al.	—	2018	→
Does exercise augment operant and Pavlovian extinction: A meta-analysis.	Roquet RF et al.	—	2018	→
Effects of intra-accumbal or intra-prefrontal cortex microinjections of adenosine 2A receptor ligands on responses to cocaine reward and seeking in rats.	Wydra K et al.	—	2018	→
Environmental enrichment enhances conditioned place preference to ethanol via an oxytocinergic-dependent mechanism in male mice.	Rae M et al.	—	2018	→
Mechanisms Underlying the Risk to Develop Drug Addiction, Insights From Studies in <i>Drosophila melanogaster</i>.	Ryvkin J et al.	—	2018	→
Metabotropic Glutamate Receptors 2 and 3 as Targets for Treating Nicotine Addiction.	Cross AJ et al.	—	2018	→
Oxytocin and Rodent Models of Addiction.	Leong KC et al.	—	2018	→
Sex differences in the nicotinic acetylcholine and dopamine receptor systems underlying tobacco smoking addiction.	Verplaetse TL et al.	—	2018	→
The effect of laboratory manipulations of negative affect on alcohol craving and use: A meta-analysis.	Bresin K et al.	—	2018	→
The neurokinin-1 receptor mediates escalated alcohol intake induced by multiple drinking models.	Sequeira MK et al.	—	2018	→
The role of hippocampal adult neurogenesis in methamphetamine addiction.	Takashima Y et al.	—	2018	→
Transcriptional and physiological adaptations in nucleus accumbens somatostatin interneurons that regulate behavioral responses to cocaine.	Ribeiro EA et al.	—	2018	→
Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability.	Miller ML et al.	—	2018	→
Acute stress worsens the deficits in appetitive behaviors for social and sexual stimuli displayed by rats after long-term withdrawal from morphine.	Bai Y et al.	—	2017	→
Addiction: A dysregulation of satiety and inflammatory processes.	Harricharan R et al.	—	2017	→
A preclinical model for identifying rats at risk of alcohol use disorder.	Jadhav KS et al.	—	2017	→
Central amygdala relaxin-3/relaxin family peptide receptor 3 signalling modulates alcohol seeking in rats.	Walker LC et al.	—	2017	→
Cigarette smoking and depression comorbidity: systematic review and proposed theoretical model.	Mathew AR et al.	—	2017	→
Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial.	Ray LA et al.	—	2017	→
Imaging corticotropin-releasing-factor and nociceptin in addiction and PTSD models.	Tollefson S et al.	—	2017	→
Is the concept of compulsion useful in the explanation or description of addictive behaviour and experience?	Heather N	—	2017	→
Neuromodulation interventions for addictive disorders: challenges, promise, and roadmap for future research.	Spagnolo PA et al.	—	2017	→
Oxytocin, Tolerance, and the Dark Side of Addiction.	Pedersen CA	—	2017	→
Pathological Overeating: Emerging Evidence for a Compulsivity Construct.	Moore CF et al.	—	2017	→
Src-dependent phosphorylation of μ-opioid receptor at Tyr<sup>336</sup> modulates opiate withdrawal.	Zhang L et al.	—	2017	→
Synaptic targets: Chronic alcohol actions.	Roberto M et al.	—	2017	→
The consummatory and motivational behaviors for natural rewards following long-term withdrawal from morphine: no anhedonia but persistent maladaptive behaviors for high-value rewards.	Li Y et al.	—	2017	→
All Roads Lead to the miRNome: miRNAs Have a Central Role in the Molecular Pathophysiology of Psychiatric Disorders.	O'Connor RM et al.	—	2016	→
A Simple Way to Measure Alterations in Reward-seeking Behavior Using Drosophila melanogaster.	Zer S et al.	—	2016	→
Association of comorbid psychopathology with the duration of cannabis use disorders.	Farmer RF et al.	—	2016	→
Belief in Food Addiction and Obesity-Related Policy Support.	Schulte EM et al.	—	2016	→
CaM Kinases: From Memories to Addiction.	Müller CP et al.	—	2016	→
Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.	Morais-Silva G et al.	—	2016	→
Cortical inhibition within motor and frontal regions in alcohol dependence post-detoxification: A pilot TMS-EEG study.	Naim-Feil J et al.	—	2016	→
Exaggerated acquisition and resistance to extinction of avoidance behavior in treated heroin-dependent men.	Sheynin J et al.	—	2016	→
Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research.	Bujarski S et al.	—	2016	→
How Preclinical Models Evolved to Resemble the Diagnostic Criteria of Drug Addiction.	Belin-Rauscent A et al.	—	2016	→
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations.	Morais-Silva G et al.	—	2016	→
Nalmefene for the management of alcohol dependence: review on its pharmacology, mechanism of action and meta-analysis on its clinical efficacy.	Mann K et al.	—	2016	→
Persistent adaptation by chronic alcohol is facilitated by neuroimmune activation linked to stress and CRF.	Breese GR et al.	—	2016	→
Reduced Social Network Drinking is Associated with Improved Response Inhibition in Women During Early Recovery from Alcohol Use Disorders: A Pilot Study.	McCutcheon VV et al.	—	2016	→
Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites.	Knapp DJ et al.	—	2016	→
Stress differentially regulates brain expression of corticotropin-releasing factor in binge-like eating prone and resistant female rats.	Calvez J et al.	—	2016	→
Systemic Delivery of a Brain-Penetrant TrkB Antagonist Reduces Cocaine Self-Administration and Normalizes TrkB Signaling in the Nucleus Accumbens and Prefrontal Cortex.	Verheij MM et al.	—	2016	→
The neurocircuitry involved in oxytocin modulation of methamphetamine addiction.	Baracz SJ et al.	—	2016	→
The Role of Cannabinoids in Neuroanatomic Alterations in Cannabis Users.	Lorenzetti V et al.	—	2016	→
The Zebrafish, a Novel Model Organism for Screening Compounds Affecting Acute and Chronic Ethanol-Induced Effects.	Tran S et al.	—	2016	→
Toward a systems-oriented approach to the role of the extended amygdala in adaptive responding.	Waraczynski M	—	2016	→
Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications.	Pei Y et al.	—	2016	→
Withdrawal from Chronic Nicotine Exposure Produces Region-Specific Tolerance to Alcohol-Stimulated GluA1 Phosphorylation.	McGinn MA et al.	—	2016	→
Alcohol use disorder with and without stimulant use: brain morphometry and its associations with cigarette smoking, cognition, and inhibitory control.	Pennington DL et al.	—	2015	→
A risk and maintenance model for bulimia nervosa: From impulsive action to compulsive behavior.	Pearson CM et al.	—	2015	→
Binge alcohol drinking elicits persistent negative affect in mice.	Lee KM et al.	—	2015	→
Brain pathways to recovery from alcohol dependence.	Cui C et al.	—	2015	→
Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking.	Leão RM et al.	—	2015	→
Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift: Dopamine for Dinner?	Blum K et al.	—	2015	→
Compulsive-like responding for opioid analgesics in rats with extended access.	Wade CL et al.	—	2015	→
Differential involvement of anxiety and novelty preference levels on oral ethanol consumption in rats.	Pelloux Y et al.	—	2015	→
Divergent regulation of distinct glucocorticoid systems in alcohol dependence.	Edwards S et al.	—	2015	→
Dopamine D1 receptor blockade impairs alcohol seeking without reducing dorsal striatal activation to cues of alcohol availability.	Fanelli RR et al.	—	2015	→
Dorsal hippocampal NMDA receptor blockade impairs extinction of naloxone-precipitated conditioned place aversion in acute morphine-treated rats by suppressing ERK and CREB phosphorylation in the basolateral amygdala.	Wang WS et al.	—	2015	→
Enhancing glutamatergic transmission during adolescence reverses early-life stress-induced deficits in the rewarding effects of cocaine in rats.	O'Connor RM et al.	—	2015	→
Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.	Befort K	—	2015	→
Metabotropic Glutamate Receptor 7 (mGluR7) as a Target for the Treatment of Psychostimulant Dependence.	Li X et al.	—	2015	→
Negative mood reverses devaluation of goal-directed drug-seeking favouring an incentive learning account of drug dependence.	Hogarth L et al.	—	2015	→
Phosphorylation of the N-methyl-d-aspartate receptor is increased in the nucleus accumbens during both acute and extended morphine withdrawal.	Anderson EM et al.	—	2015	→
Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats.	Tian YE et al.	—	2015	→
The dark side of emotion: the addiction perspective.	Koob GF	—	2015	→
The Molecular Neurobiology of Twelve Steps Program & Fellowship: Connecting the Dots for Recovery.	Blum K et al.	—	2015	→
The role of serotonin in drug use and addiction.	Müller CP et al.	—	2015	→
Acute total sleep deprivation potentiates cocaine-induced hyperlocomotion in mice.	Berro LF et al.	—	2014	→
Addiction as a stress surfeit disorder.	Koob GF et al.	—	2014	→
Allostasis as a conceptual framework linking bipolar disorder and addiction.	Pettorruso M et al.	—	2014	→
Complex motivated behaviors for natural rewards following a binge-like regimen of morphine administration: mixed phenotypes of anhedonia and craving after short-term withdrawal.	Bai Y et al.	—	2014	→
Drug withdrawal conceptualized as a stressor.	Chartoff EH et al.	—	2014	→
Individual differences in attentional bias associated with cocaine dependence are related to varying engagement of neural processing networks.	Kilts CD et al.	—	2014	→
Induction of depressive-like effects by subchronic exposure to cocaine or heroin in laboratory rats.	Zilkha N et al.	—	2014	→
Involvement of glutamatergic and GABAergic systems in nicotine dependence: Implications for novel pharmacotherapies for smoking cessation.	Li X et al.	—	2014	→
It's MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system.	Chartoff EH et al.	—	2014	→
Morphine Reduces Expression of TRPV1 Receptors in the Amygdala but not in the Hippocampus of Male Rats.	Hakimizadeh E et al.	—	2014	→
Mutation of putative GRK phosphorylation sites in the cannabinoid receptor 1 (CB1R) confers resistance to cannabinoid tolerance and hypersensitivity to cannabinoids in mice.	Morgan DJ et al.	—	2014	→
Neurobiological mechanisms that contribute to stress-related cocaine use.	Mantsch JR et al.	—	2014	→
Obsessive-compulsive aspects and pathological gambling in an Italian sample.	Petruccelli F et al.	—	2014	→
Rodent models for compulsive alcohol intake.	Hopf FW et al.	—	2014	→
Sex differences in the neurobiology of drug addiction.	Bobzean SA et al.	—	2014	→
The development and maintenance of drug addiction.	Wise RA et al.	—	2014	→
The neurokinin-1 receptor in addictive processes.	Schank JR	—	2014	→
Ultrasonic vocalizations: evidence for an affective opponent process during cocaine self-administration.	Barker DJ et al.	—	2014	→
Addiction is a Reward Deficit and Stress Surfeit Disorder.	Koob GF	—	2013	→
Alterations in ethanol seeking and self-administration following yohimbine in selectively bred alcohol-preferring (P) and high alcohol drinking (HAD-2) rats.	Bertholomey ML et al.	—	2013	→
Amygdalostriatal projections in the neurocircuitry for motivation: a neuroanatomical thread through the career of Ann Kelley.	Zorrilla EP et al.	—	2013	→
A phenotypic structure and neural correlates of compulsive behaviors in adolescents.	Montigny C et al.	—	2013	→
A selective insular perfusion deficit contributes to compromised salience network connectivity in recovering alcoholic men.	Sullivan EV et al.	—	2013	→
Cocaine-induced membrane adaptation in the central nucleus of amygdala.	Chen B et al.	—	2013	→
Corticotropin-releasing factor in the mouse central nucleus of the amygdala: ultrastructural distribution in NMDA-NR1 receptor subunit expressing neurons as well as projection neurons to the bed nucleus of the stria terminalis.	Beckerman MA et al.	—	2013	→
CRF-CRF1 receptor system in the central and basolateral nuclei of the amygdala differentially mediates excessive eating of palatable food.	Iemolo A et al.	—	2013	→
Development of κ opioid receptor antagonists.	Carroll FI et al.	—	2013	→
Efficacy of psychostimulant drugs for amphetamine abuse or dependence.	Pérez-Mañá C et al.	—	2013	→
Escalation of drug self-administration as a hallmark of persistent addiction liability.	Edwards S et al.	—	2013	→
Kappa opioid receptors regulate stress-induced cocaine seeking and synaptic plasticity.	Graziane NM et al.	—	2013	→
Modification of anxiety-like behaviors by nociceptin/orphanin FQ (N/OFQ) and time-dependent changes in N/OFQ-NOP gene expression following ethanol withdrawal.	Aujla H et al.	—	2013	→
Morphine dependence is associated with changes in neuropeptide S receptor expression and function in rat brain.	Ghazal P et al.	—	2013	→
Negative reinforcement in drug addiction: the darkness within.	Koob GF	—	2013	→
Neuroadaptive changes associated with smoking: structural and functional neural changes in nicotine dependence.	Martin-Soelch C	—	2013	→
Neuroimaging the temporal dynamics of human avoidance to sustained threat.	Schlund MW et al.	—	2013	→
Oxytocin modulates dopamine-mediated reward in the rat subthalamic nucleus.	Baracz SJ et al.	—	2013	→
Pain and suicidality: insights from reward and addiction neuroscience.	Elman I et al.	—	2013	→
Paternal deprivation alters the development of catecholaminergic innervation in the prefrontal cortex and related limbic brain regions.	Braun K et al.	—	2013	→
Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?	Aznar S et al.	—	2013	→
Relationship of Internet addiction with impulsivity and severity of psychopathology among Turkish university students.	Dalbudak E et al.	—	2013	→
Rimonabant precipitates anxiety in rats withdrawn from palatable food: role of the central amygdala.	Blasio A et al.	—	2013	→
Social influences on morphine conditioned place preference in adolescent mice.	Cole SL et al.	—	2013	→
Subjective response to alcohol among alcohol-dependent individuals: effects of the μ-opioid receptor (OPRM1) gene and alcoholism severity.	Ray LA et al.	—	2013	→
The downward spiral of chronic pain, prescription opioid misuse, and addiction: cognitive, affective, and neuropsychopharmacologic pathways.	Garland EL et al.	—	2013	→
The frustrating effects of just missing the jackpot: slot machine near-misses trigger large skin conductance responses, but no post-reinforcement pauses.	Dixon MJ et al.	—	2013	→
The influences of reproductive status and acute stress on the levels of phosphorylated delta opioid receptor immunoreactivity in rat hippocampus.	Burstein SR et al.	—	2013	→
The role of the neuropeptide S system in addiction: focus on its interaction with the CRF and hypocretin/orexin neurotransmission.	Cannella N et al.	—	2013	→
When a TRP goes bad: transient receptor potential channels in addiction.	Wescott SA et al.	—	2013	→
Withdrawal from extended-access cocaine self-administration results in dysregulated functional activity and altered locomotor activity in rats.	Calipari ES et al.	—	2013	→
A brain on cannabinoids: the role of dopamine release in reward seeking.	Oleson EB et al.	—	2012	→
Antagonism of sigma-1 receptors blocks compulsive-like eating.	Cottone P et al.	—	2012	→
Are executive function and impulsivity antipodes? A conceptual reconstruction with special reference to addiction.	Bickel WK et al.	—	2012	→
A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch.	Berlin I et al.	—	2012	→
Cocaine withdrawal causes delayed dysregulation of stress genes in the hippocampus.	García-Fuster MJ et al.	—	2012	→
Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process.	Walker BM	—	2012	→
Current progress in pharmacologic treatment strategies for alcohol dependence.	Clapp P	—	2012	→
Does food addiction exist? A phenomenological discussion based on the psychiatric classification of substance-related disorders and addiction.	Albayrak O et al.	—	2012	→
Drug withdrawal-induced depression: serotonergic and plasticity changes in animal models.	Renoir T et al.	—	2012	→
Guanfacine effects on stress, drug craving and prefrontal activation in cocaine dependent individuals: preliminary findings.	Fox HC et al.	—	2012	→
"Hooked on" prescription-type opiates prior to using heroin: results from a survey of syringe exchange clients.	Peavy KM et al.	—	2012	→
Long-term changes in reward-seeking following morphine withdrawal are associated with altered N-methyl-D-aspartate receptor 1 splice variants in the amygdala.	Anderson EM et al.	—	2012	→
Neuropeptide modulation of central amygdala neuroplasticity is a key mediator of alcohol dependence.	Gilpin NW et al.	—	2012	→
Role of IKK/NF-κB signaling in extinction of conditioned place aversion memory in rats.	Yang CH et al.	—	2012	→
Schedule-induced polydipsia as a model of compulsive behavior: neuropharmacological and neuroendocrine bases.	Moreno M et al.	—	2012	→
Sexual deprivation increases ethanol intake in Drosophila.	Shohat-Ophir G et al.	—	2012	→
Smoking withdrawal is associated with increases in brain activation during decision making and reward anticipation: a preliminary study.	Addicott MA et al.	—	2012	→
Stress and addiction: contribution of the corticotropin releasing factor (CRF) system in neuroplasticity.	Haass-Koffler CL et al.	—	2012	→
The detrimental effects of emotional process dysregulation on decision-making in substance dependence.	Murphy A et al.	—	2012	→
The endocannabinoid system modulates the valence of the emotion associated to food ingestion.	Méndez-Díaz M et al.	—	2012	→
Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat.	Economidou D et al.	—	2011	→
Activation of D₂-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior.	Xue Y et al.	—	2011	→
A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development.	Juster RP et al.	—	2011	→
Changes of protein expression profiles in the amygdala during the process of morphine-induced conditioned place preference in rats.	Lin X et al.	—	2011	→
Chronic alcohol neuroadaptation and stress contribute to susceptibility for alcohol craving and relapse.	Breese GR et al.	—	2011	→
Cocaine self-administration leads to alterations in temporal responses to cocaine challenge in limbic and motor circuitry.	Chen YI et al.	—	2011	→
Development of ethanol withdrawal-related sensitization and relapse drinking in mice selected for high- or low-ethanol preference.	Lopez MF et al.	—	2011	→
Discrete cue-conditioned alcohol-seeking after protracted abstinence: pattern of neural activation and involvement of orexin₁ receptors.	Jupp B et al.	—	2011	→
Effects of corticotropin-releasing hormone receptor antagonists on the ethanol-induced increase of dynorphin A1-8 release in the rat central amygdala.	Lam MP et al.	—	2011	→
Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors.	Serrano A et al.	—	2011	→
Escalation patterns of varying periods of heroin access.	Vendruscolo LF et al.	—	2011	→
Ethanol modulation of synaptic plasticity.	McCool BA	—	2011	→
Human avoidance and approach learning: evidence for overlapping neural systems and experiential avoidance modulation of avoidance neurocircuitry.	Schlund MW et al.	—	2011	→
Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long-Evans rats by the α-2 adrenoreceptor antagonist yohimbine.	Simms JA et al.	—	2011	→
In vivo ethanol experience increases D(2) autoinhibition in the ventral tegmental area.	Perra S et al.	—	2011	→
Markov model of smoking cessation.	Killeen PR	—	2011	→
Neural Changes Developed during the Extinction of Cocaine Self-Administration Behavior.	Higuera-Matas A et al.	—	2011	→
Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: a hypothesis.	Blum K et al.	—	2011	→
Orexin Receptor Targets for Anti-Relapse Medication Development in Drug Addiction.	Zhou L et al.	—	2011	→
Overexpression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats.	Larson EB et al.	—	2011	→
Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems.	Smith AW et al.	—	2011	→
The effect of pain on stroop performance in patients with opiate dependence in sustained remission.	Aniskin DB et al.	—	2011	→
What kinds of things are psychiatric disorders?	Kendler KS et al.	—	2011	→
A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in Caenorhabditis elegans.	Mitchell P et al.	—	2010	→
Alcohol response and consumption in adolescent rhesus macaques: life history and genetic influences.	Schwandt ML et al.	—	2010	→
Amygdala involvement in human avoidance, escape and approach behavior.	Schlund MW et al.	—	2010	→
Behavioral and functional evidence of metabotropic glutamate receptor 2/3 and metabotropic glutamate receptor 5 dysregulation in cocaine-escalated rats: factor in the transition to dependence.	Hao Y et al.	—	2010	→
Behavioral effects of withdrawal from sweetened vegetable shortening in rats.	McGee HM et al.	—	2010	→
Compulsive use of dopaminergic drug therapy in Parkinson's disease: reward and anti-reward.	Evans AH et al.	—	2010	→
Converging action of alcohol consumption and cannabinoid receptor activation on adult hippocampal neurogenesis.	Alén F et al.	—	2010	→
Dynorphin, stress, and depression.	Knoll AT et al.	—	2010	→
Effects of extended cocaine access and cocaine withdrawal on choice between cocaine and food in rhesus monkeys.	Banks ML et al.	—	2010	→
Effects of galanin on monoaminergic systems and HPA axis: Potential mechanisms underlying the effects of galanin on addiction- and stress-related behaviors.	Picciotto MR et al.	—	2010	→
Ethanol action on dopaminergic neurons in the ventral tegmental area: interaction with intrinsic ion channels and neurotransmitter inputs.	Morikawa H et al.	—	2010	→
Evaluation of the relationship between anxiety during withdrawal and stress-induced reinstatement of cocaine seeking.	Erb S	—	2010	→
Hedonic and motivational roles of opioids in food reward: implications for overeating disorders.	Peciña S et al.	—	2010	→
"I Always Kept a Job": Income Generation, Heroin Use and Economic Uncertainty in 21st Century Detroit.	Draus PJ et al.	—	2010	→
Low doses of cocaine decrease, and high doses increase, anxiety-like behavior and brain progestogen levels among intact rats.	Kohtz AS et al.	—	2010	→
Muscarinic type 2 receptors in the lateral dorsal tegmental area modulate cocaine and food seeking behavior in rats.	Shabani S et al.	—	2010	→
Neurobiology of dysregulated motivational systems in drug addiction.	Edwards S et al.	—	2010	→
Neurocircuitry of addiction.	Koob GF et al.	—	2010	→
Neuroplastic alterations in the limbic system following cocaine or alcohol exposure.	Stuber GD et al.	—	2010	→
Nothing to fear? Neural systems supporting avoidance behavior in healthy youths.	Schlund MW et al.	—	2010	→
Sex differences and ovarian hormones in animal models of drug dependence.	Carroll ME et al.	—	2010	→
Sleep disturbance as a universal risk factor for relapse in addictions to psychoactive substances.	Brower KJ et al.	—	2010	→
The mGluR2 positive allosteric modulator BINA decreases cocaine self-administration and cue-induced cocaine-seeking and counteracts cocaine-induced enhancement of brain reward function in rats.	Jin X et al.	—	2010	→
The role of functional postsynaptic NMDA receptors in the central nucleus of the amygdala in opioid dependence.	Glass MJ	—	2010	→
The role of progestins in the behavioral effects of cocaine and other drugs of abuse: human and animal research.	Anker JJ et al.	—	2010	→
What neurobiology tells us about addiction.	Iguchi MY et al.	—	2010	→
Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models.	Schramm-Sapyta NL et al.	—	2009	→
Brain stress systems in the amygdala and addiction.	Koob GF	—	2009	→
Deletion of vanilloid receptor (TRPV1) in mice alters behavioral effects of ethanol.	Blednov YA et al.	—	2009	→
Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory.	Koob GF	—	2009	→
Effects of chronic intracerebroventricular 3,4-methylenedioxy-N-methamphetamine (MDMA) or fluoxetine on the active avoidance test in rats with or without exposure to mild chronic stress.	León LA et al.	—	2009	→
[Gamma-hydroxybutyric acid (GHB): more than a date rape drug, a potentially addictive drug].	Karila L et al.	—	2009	→
Gene expression changes following extinction testing in a heroin behavioral incubation model.	Kuntz-Melcavage KL et al.	—	2009	→
Genetical genomic determinants of alcohol consumption in rats and humans.	Tabakoff B et al.	—	2009	→
Intrinsic neuronal plasticity in the juxtacapsular nucleus of the bed nuclei of the stria terminalis (jcBNST).	Francesconi W et al.	—	2009	→
kappa-Opioid receptor signaling and brain reward function.	Bruijnzeel AW	—	2009	→
Management of opioid medications in patients with chronic pain and risk of substance misuse.	Savage SR	—	2009	→
Measurement of affective state during chronic nicotine treatment and withdrawal by affective taste reactivity in mice: the role of endocannabinoids.	Wing VC et al.	—	2009	→
Neurogenetics of dopaminergic receptor supersensitivity in activation of brain reward circuitry and relapse: proposing "deprivation-amplification relapse therapy" (DART).	Blum K et al.	—	2009	→
Reward processing by the opioid system in the brain.	Le Merrer J et al.	—	2009	→
Hedonic Homeostatic Dysregulation as a Driver of Drug-Seeking Behavior.	Koob GF	—	2008	→