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Cited by 500Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesParkinson's Disease Mechanisms and Treatments

Roles for nigrostriatal—not just mesocorticolimbic—dopamine in reward and addiction

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Wise, Roy A.·2009·Trends in Neurosciences
DOI 10.1016/j.tins.2009.06.004PMC PMC2755633
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Abstract

Forebrain dopamine circuitry has traditionally been studied by two largely independent specialist groups: students of Parkinson’s disease who study the nigrostriatal dopamine system that originates in the substantia nigra (SN), and students of motivation and addiction who study the role of the mesolimbic and mesocortical dopamine systems that originate in the ventral tegmental area (VTA). The anatomical evidence for independent nigrostriatal and mesolimbic dopamine systems has, however, long been obsolete. There is now compelling evidence that both nominal “systems” participate in reward function and addiction. Electrical stimulation of both SN and VTA is rewarding, blockade of glutamatergic or cholinergic input to either SN or VTA attenuates the habit-forming effects of intravenous cocaine, and dopamine in both nigrostriatal and mesocorticolimbic terminal fields participates in the defining property of rewarding events: the reinforcement of memory consolidation. Thus the similarities between nigrostriatal and mesolimbic dopamine systems may be as important as their differences.

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  • The ascending mesocorticostriatal dopamine system has a key role in the rewarding properties of nearly all drugs of abuse.

    “A principal focus of research on the neurobiology of the rewarding effects of abused drugs has been the origins and terminal areas of the ascending mesocorticostriatal dopamine systems that have a key role in the rewarding properties of nearly all drugs of abuse (table 1).”

    From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [34]

    The Introduction and Summary and conclusions describe dopamine as important to reward and addiction, and Intravenous cocaine reward gives evidence for its role in cocaine reward. The paper also emphasizes that nigrostriatal dopamine matters, not just mesocorticolimbic dopamine. Our copy does not establish the claim’s scope of “nearly all drugs of abuse.” No page numbers were provided for these passages. (LLM, conf=0.84)

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  • The DAergic system, particularly the mesocorticolimbic pathway, is involved in drug addiction because DA modulates limbic and cortical sites for goal-directed behavior.

    “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 [29]

  • The striatum is implicated in the rewarding and addictive effects of nicotine.

    “a region implicated in the rewarding and addictive effects of nicotine (Wise, 2009;Changeux, 2010).”

    From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as Wise, 2009

  • Nicotine exerts its rewarding effects by acting at nAChRs and increasing neurotransmission in the mesolimbic and nigrostriatal dopaminergic pathways.

    “Nicotine seems to exert its rewarding effects by acting at nicotinic acetylcholine receptors (nAChRs) and increasing neurotransmission in the mesolimbic and nigrostriatal dopa-minergic pathways”

    From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as Wise, 2009

  • Varenicline's action at α6β2* nAChRs may contribute to its efficacy as a smoking cessation aid.

    “these observations may suggest that varenicline's action at ␣6␤2* nAChRs contributes to its efficacy as a smoking cessation aid.”

    From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as Wise, 2009

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Research works printed but not linked: 1

  1. [6]Fallon JH Loughlin SE Paxinos G 1995 Substantia Nigra The rat nervous system 2 215 237 Academic Press

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Authors
Wise, R. A.
Affiliations
National Institutes of Health (US)
Corresponding author
Wise, Roy A.
ORCID
Wise, Roy A.
Venue
Trends in Neurosciences
Publisher
Elsevier BV
Published
2009-10
Volume
32
Issue
10
Pages
517-524
ISSN
0166-2236 (ISSN-L)
DOI
10.1016/j.tins.2009.06.004
PMC
PMC2755633
OpenAlex
W1978702556
Semantic Scholar
e5a7527e7aecdda634d18db1325d21c7fd4667ce
Cited by
500
References
96
Citations by year
2026: 10 · 2025: 23 · 2024: 25 · 2023: 24 · 2022: 30 · 2021: 30 · 2020: 35 · 2019: 23 · 2018: 22 · 2017: 32 · 2016: 48 · 2015: 28 · 2014: 33 · 2013: 41 · 2012: 45
FWCI
2.76
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Neurosciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health
  • National Institute on Drug Abuse (Z01DA000471)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
nigrostriatal dopamine system, mesolimbic dopamine system, mesocortical dopamine system, substantia nigra, ventral tegmental area, reward, addiction, cocaine, habit formation, memory consolidation, glutamatergic input, cholinergic input, Parkinson's disease
MeSH terms
Animals, Cerebral Cortex, Cocaine, Corpus Striatum, Dopamine, Humans, Infusions, Intravenous, Microinjections, Neural Pathways, Reinforcement, Psychology, Reward, Self Stimulation, Substantia Nigra, Behavior, Addictive, Ventral Tegmental Area, Long-Term Potentiation, Dopamine Agonists, Dopamine Antagonists, Long-Term Synaptic Depression

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