ReviewThe American journal of psychiatry2005
The neural basis of addiction: a pathology of motivation and choice.
Review in The American journal of psychiatry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1,263 papers, 7 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Charleston ARC Clinical Project 4 Cortical rTMS as a Tool to Change Craving and Brain Reactivity to Alcohol Cues
Theta Burst TMS as a Tool to Change Smoking Behavior
Who cites it
1,263 citing papers in PubMed, 7 syntheses or guidelines pooled it, 2,764 citations in OpenAlex.
- Ketamine for substance use disorders: a systematic review and meta-analysis.Frontiers in psychiatry · 2026Pooled it
- Neurometabolite Alterations Associated With Cannabis Use: A Proton Magnetic Resonance Spectroscopy Meta-Analysis.Human brain mapping · 2025Pooled it
- Oral and Long-acting Injectable Aripiprazole in Severe Mental Illness and Substance Use Disorder Comorbidity: An Updated Systematic Review.Current neuropharmacology · 2025Pooled it
- The structural and functional brain alternations in tobacco use disorder: a systematic review and meta-analysis.Frontiers in psychiatry · 2025Pooled it
- Self-management with alcohol over lifespan: psychological mechanisms, neurobiological underpinnings, and risk assessment.Molecular psychiatry · 2023Pooled it
- A systematic review of the perceptions and attitudes of mental health nurses towards alcohol and other drug use in mental health clients.International journal of mental health nursing · 2022Pooled it
- Distinct brain structural abnormalities in attention-deficit/hyperactivity disorder and substance use disorders: A comparative meta-analysis.Translational psychiatry · 2022Pooled it
- Reward, relief, and habit drinking profiles in treatment seeking individuals with an AUD.Alcohol and alcoholism (Oxford, Oxfordshire) · 2024Trial
- N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- GutGut microbes · 2026Article
- Dissociation of decision-making from escalated drug intake within a long-access model.Behavioural brain research · 2026Article
- Effort, timing and choice: a refined rodent effort choice task with excellent sensitivity to dopamine modulators.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Changing the motivation for mental work with temporal interference stimulation.Translational psychiatry · 2026Article
- Nucleus accumbens CD81 regulates methamphetamine-induced locomotor activity, conditioned reward, and reinstatement in male and female rats.Psychopharmacology · 2026Article
- Review
- Intermittent and extended cocaine access attenuate cocaine-vs-food choice in male and female rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Reward Prediction Errors Drive Reinforcement Learning and Recognition Memory: Gender Differences in Methamphetamine Abusers.Brain and behavior · 2026Article
- Effects of working memory and reward reactivity on externalizing behaviors in the ABCD study.Developmental cognitive neuroscience · 2026Article
- Acetazolamide inhibition of carbonic anhydrase 4 reverses opioid-induced synaptic rearrangements in nucleus accumbens and reduces drug-seeking behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Impact of Voluntary Alcohol Consumption on Corticostriatal Plasticity in Rats.The European journal of neuroscience · 2026Article
1,203 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveA primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs. In this review the authors explore how advances in neurobiology are approaching an understanding of the cellular and circuitry underpinnings of addiction, and they describe the novel pharmacotherapeutic targets emerging from this understanding.
methodFindings from neuroimaging of addicts are integrated with cellular studies in animal models of drug seeking.
resultsWhile dopamine is critical for acute reward and initiation of addiction, end-stage addiction results primarily from cellular adaptations in anterior cingulate and orbitofrontal glutamatergic projections to the nucleus accumbens. Pathophysiological plasticity in excitatory transmission reduces the capacity of the prefrontal cortex to initiate behaviors in response to biological rewards and to provide executive control over drug seeking. Simultaneously, the prefrontal cortex is hyperresponsive to stimuli predicting drug availability, resulting in supraphysiological glutamatergic drive in the nucleus accumbens, where excitatory synapses have a reduced capacity to regulate neurotransmission.
conclusionsCellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control (choice), and enhancing glutamatergic drive in response to drug-associated stimuli.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.