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Distinct Roles of Synaptic Transmission in Direct and Indirect Striatal Pathways to Reward and Aversive Behavior
Open accessAbstract
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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“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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Metadata
- 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
- ORCID
- Hikida, Takatoshi
- 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
- bronze
- doi.org
- Licence
- 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 › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- 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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