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Brain reward circuitry beyond the mesolimbic dopamine system: A neurobiological theory
Open accessAbstract
Reductionist attempts to dissect complex mechanisms into simpler elements are necessary, but not sufficient for understanding how biological properties like reward emerge out of neuronal activity. Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures-the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle. In addition, studies found roles of non-dopaminergic mechanisms of the supramammillary, rostromedial tegmental and midbrain raphe nuclei in reward. To explain intracranial self-administration and related effects of various drug manipulations, I outlined a neurobiological theory claiming that there is an intrinsic central process that coordinates various selective functions (including perceptual, visceral, and reinforcement processes) into a global function of approach. Further, this coordinating process for approach arises from interactions between brain structures including those structures mentioned above and their closely linked regions: the medial prefrontal cortex, septal area, ventral pallidum, bed nucleus of stria terminalis, preoptic area, lateral hypothalamic areas, lateral habenula, periaqueductal gray, laterodorsal tegmental nucleus and parabrachical area.
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“The role of the DAergic system (in particular the mesocorticolimbic pathway) in drug addiction derives from DA’s ability to modulate many of the limbic and cortical sites involved in goal-directed behavior (Fig. 1) [18, 28–31].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [30]
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“Studies conducted in recent years have identified the LHb as a source of anti-reward signals that plays an important role in determining the reward-related activity of DA neurons [18, 30, 68–70].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [30]
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“In addition, reward is an induced internal state that produces and reinforces approach behavior [3,4].”
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Metadata
- Authors
- Ikemoto, S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Ikemoto, Satoshi
- ORCID
- Ikemoto, Satoshi
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 35
- Issue
- 2
- Pages
- 129-150
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC2894302
- OpenAlex
- W2026626196
- Cited by
- 454
- References
- 277
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 26 · 2023: 22 · 2022: 39 · 2021: 33 · 2020: 35 · 2019: 31 · 2018: 24 · 2017: 13 · 2016: 23 · 2015: 31 · 2014: 33 · 2013: 35 · 2012: 32
- FWCI
- 13.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (ZIADA000480, Z01DA000439, ZIADA000439)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain reward system, mesolimbic dopamine system, drug reward, supramammillary nucleus, rostromedial tegmental nucleus, midbrain raphe nuclei, approach behavior, reinforcement, medial prefrontal cortex, septal area, ventral pallidum, bed nucleus of the stria terminalis, preoptic area, lateral hypothalamus, lateral habenula, periaqueductal gray, laterodorsal tegmental nucleus, parabrachial area
- MeSH terms
- Animals, Brain, Dopamine, Models, Neurological, Neural Pathways, Reward, Self Administration
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