Cocaine-induced adaptations in D1 and D2 accumbens projection neurons (a dichotomy not necessarily synonymous with direct and indirect pathways)
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Cocaine exposure causes enduring neuroadaptations in ventral striatum, or nucleus accumbens (NAc), an area critically involved in reward learning and relapse of drug seeking. Medium spiny neurons (MSNs) in striatum are dichotomous in their expression of either D1 or D2 dopamine receptors, along with other receptors and neuropeptides. In dorsal striatum, these two subpopulations show non-overlapping innervation of distinct terminal fields via the direct or indirect pathways. However, NAc D1-MSNs and D2-MSNs are not fully segregated in this manner, with both cell types innervating ventral pallidum. Recent studies show that D1-MSNs and D2-MSNs play opposing roles in cocaine-associated behaviors. Further, cocaine induces differential adaptations in these two subpopulations in NAc, including changes to synaptic plasticity, glutamatergic signaling, and spine morphology.
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The nucleus accumbens core and dorsolateral regions project mainly to the dorsolateral ventral pallidum and substantia nigra, while the medial shell projects mainly to the ventromedial ventral pallidum and ventral tegmental area.
“NAc core and dorsolateral regions of the NAc project mainly to the dorsolateral VP and substantia nigra (SN) while NAc medial shell projects mainly to the ventromedial VP and VTA (20).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [20]
D1 medium spiny neurons project to the ventral tegmental area and ventral pallidum, while D2 medium spiny neurons project to the ventral pallidum.
“NAc D1-MSN and D2-MSNs are also distinguished by their projections to target regions: D1-MSNs target the ventral tegmental area (VTA) and ventral pallidum (VP), while D2-MSNs specifically target the VP (FIGURE 1) (19–21).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [20]
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References 59 · Cited by 272
- Authors
- Smith, R. J., Lobo, M. K., Spencer, S., & Kalivas, P. W.
- Affiliations
- Medical University of South Carolina (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Kalivas, Peter W
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 23
- Issue
- 4
- Pages
- 546-552
- ISSN
- 0959-4388 (ISSN-L)
- PMC
- PMC3681928
- OpenAlex
- W2011629807
- Cited by
- 272
- References
- 59
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 17 · 2023: 21 · 2022: 14 · 2021: 23 · 2020: 12 · 2019: 26 · 2018: 25 · 2017: 26 · 2016: 26 · 2015: 34 · 2014: 19 · 2013: 10
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 DA03906, R01 DA12513, P50 DA015369, F32 DA031519)
- 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
- cocaine, nucleus accumbens, medium spiny neurons, dopamine D1 receptor, dopamine D2 receptor, direct and indirect pathways, ventral pallidum, synaptic plasticity, glutamatergic signaling, dendritic spine morphology, drug-seeking behavior, reward learning, neural adaptation
- MeSH terms
- Adaptation, Physiological, Animals, Cocaine, Neural Pathways, Nucleus Accumbens, Receptors, Dopamine D1, Receptors, Dopamine D2
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