Cited by 597Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeurological disorders and treatments

Distinct Roles of Synaptic Transmission in Direct and Indirect Striatal Pathways to Reward and Aversive Behavior

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Hikida, Takatoshi, Kimura, Kensuke, Wada, Norio, Funabiki, Kazuo, Nakanishi, Shigetada·2010·Neuron

Abstract

In the basal ganglia, convergent input and dopaminergic modulation of the direct striatonigral and the indirect striatopallidal pathways are critical in rewarding and aversive learning and drug addiction. To explore how the basal ganglia information is processed and integrated through these two pathways, we developed a reversible neurotransmission blocking technique, in which transmission of each pathway was selectively blocked by specific expression of transmission-blocking tetanus toxin in a doxycycline-dependent manner. The results indicated that the coordinated modulation of these two pathways was necessary for dopamine-mediated acute psychostimulant actions. This modulation, however, shifted to the predominant roles of the direct pathway in reward learning and cocaine sensitization and the indirect pathway in aversive behavior. These two pathways thus have distinct roles: the direct pathway critical for distinguishing associative rewarding stimuli from nonassociative ones and the indirect pathway for rapid memory formation to avoid aversive stimuli.

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Crossref · 10.1016/j.neuron.2010.05.011

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  • Inhibition of striatal D2R or activation of D1R-expressing striatal neurons enhances sensitivity to the rewarding effects of drugs.

    “inhibition of striatal D2R or activation of D1R-expressing striatal neurons (which mediate signalling in the striatal direct pathway) enhance the sensitivity to the rewarding effects of drugs (71–73).”

    From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [72]

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Authors
Hikida, T., Kimura, K., Wada, N., Funabiki, K., & Nakanishi, S.
Affiliations
  • Japan Science and Technology Agency (JP)
  • Kyoto University (JP)
Corresponding author
Nakanishi, Shigetada
Venue
Neuron
Publisher
Elsevier BV
Published
2010-06
Volume
66
Issue
6
Pages
896-907
ISSN
0896-6273 (ISSN-L)
OpenAlex
W1973788414
Cited by
592
References
55
Citations by year
2026: 13 · 2025: 36 · 2024: 24 · 2023: 35 · 2022: 36 · 2021: 47 · 2020: 34 · 2019: 37 · 2018: 42 · 2017: 38 · 2016: 46 · 2015: 42 · 2014: 54 · 2013: 47 · 2012: 28
FWCI
13.95
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • Precursory Research for Embryonic Science and Technology
  • Takeda Science Foundation
  • Uehara Memorial Foundation
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
basal ganglia, dopamine, synaptic transmission, tetanus toxin, reward learning, aversive behavior, cocaine sensitization, psychostimulant effects, drug addiction
MeSH terms
Action Potentials, Adaptation, Physiological, Dependovirus, Central Nervous System Stimulants, Analysis of Variance, Animals, Avoidance Learning, Behavior, Animal, Cholera Toxin, Cocaine, Conditioning, Operant, Corpus Striatum, Doxycycline, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Methamphetamine, Mice, Transgenic, Neural Pathways, Synaptic Transmission, Neurons, Neurotoxins, Recombinant Fusion Proteins, Reward, RNA, Messenger, Substantia Nigra, Tetanus Toxin, Transfection, Proto-Oncogene Proteins c-fos, Dopamine Uptake Inhibitors, Vesicle-Associated Membrane Protein 2, Mice

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