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Cited by 21Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchSchizophrenia research and treatment

WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine

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Ceglia, Ilaria, Lee, Ko-Woon, Cahill, Michael E., Graves, Steven M., Dietz, David, Surmeier, Dalton J., Nestler, Eric J., Nairn, Angus C. +2 more·2017·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1621185114PMC PMC5307471
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Abstract

Significance: Cocaine-induced synaptic plasticity in the nucleus accumbens is implicated in neural adaptations that underlie addiction. Here we demonstrate that Wiskott-Aldrich syndrome protein (WASP) family verprolin homologous protein 1 (WAVE1) plays a selective role in medium spiny projection neurons that express D1 dopamine receptors (D1-MSNs) in the cellular and behavioral actions of cocaine. Our results suggest that chronic exposure to cocaine, followed by withdrawal, potentiates the signaling capacity of D1 dopamine and NMDA glutamate receptors, allowing WAVE1 activation in response to an acute cocaine challenge. WAVE1 activation is associated with morphological and functional decreases in glutamatergic synapses on D1-MSNs. Thus, we propose that WAVE1 is involved in a negative feedback mechanism of regulation of glutamatergic synapses as a part of the process of cocaine-induced synaptic plasticity.

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Crossref · 10.1073/pnas.1621185114

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  • Cocaine administration also reduces inhibitory phosphorylation at Ser310, 397 and 441 on WAVE1 in an NMDA receptor- or dopamine D1 receptor-dependent manner.

    “Cocaine administration also reduces inhibitory phosphorylation at Ser310, 397 and 441 on WAVE1 in an NMDA receptor- or dopamine D1 receptor-dependent manner.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [11]

    The Results report reduced phosphorylation at Ser310, Ser397, and Ser441 after an acute cocaine challenge following chronic cocaine administration and 14 days of withdrawal; D1 or NMDA receptor antagonists largely blocked the effect. The claim omits that essential regimen: the same Results section reports no significant phosphorylation change after acute or chronic cocaine administration alone. Page numbers were not supplied in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • WAVE1 is also required for cocaine-induced behavioral and synaptic plasticity.

    “WAVE1 is also required for cocaine-induced behavioral and synaptic plasticity11.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [11]

    The Discussion reports that deleting WAVE1 in D1-expressing neurons reduced cocaine place preference and maintenance of locomotor sensitization, while the Results and Discussion describe WAVE1-dependent spine and AMPA-current changes after a cocaine challenge following chronic exposure and withdrawal. But the Discussion also says WAVE1 was not required for the development of locomotor sensitization or the spine-density increase after chronic cocaine exposure. The unqualified claim is therefore broader than the findings. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • WAVE1 deletion in neurons expressing the dopamine D1 receptor but not the dopamine D2 receptor significantly decreases cocaine reward, as measured by cocaine-associated place preference and cocaine-induced sensitized locomotor behavior.

    “WAVE1 deletion in neurons expressing the dopamine D1 receptor but not the dopamine D2 receptor significantly decreases cocaine reward, as measured by cocaine-associated place preference and cocaine-induced sensitized locomotor behavior11.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [11]

    The Results report significantly reduced cocaine-conditioned place preference in WAVE1 D1-KO mice, but not D2-KO mice. They also report that both knockout groups developed locomotor sensitization; only D1-KO mice showed a lower response to a cocaine challenge after withdrawal. The claim omits that qualification and treats locomotor sensitization as a measure of reward. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • WAVE1 is a brain-enriched regulator that is especially abundant in neurons, oligodendrocyte precursor cells and mature oligodendrocytes.

    “WAVE1 is a brain-enriched regulator that is especially abundant in neurons9–12, oligodendrocyte precursor cells and mature oligodendrocytes13.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [11]

  • Alterations in CDK5 phosphorylation of WAVE1 were observed in the brains of a mouse model of Alzheimer's disease, as well as in those of cocaine-administered mice.

    “Furthermore, alterations in CDK5 phosphorylation of WAVE1 were observed in the brains of a mouse model of Alzheimer’s disease (AD)47, as well as in those of cocaine-administered mice11.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [11]

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Authors
Ceglia, I., Lee, K.-W., Cahill, M. E., Graves, S. M., Dietz, D., Surmeier, D. J., Nestler, E. J., Nairn, A. C., Greengard, P., & Kim, Y.
Affiliations
  • Rockefeller University (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Northwestern University (US)
  • University at Buffalo, State University of New York (US)
  • Yale University (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2017-01-23
Volume
114
Issue
6
Pages
1395-1400
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1621185114
PMC
PMC5307471
OpenAlex
W2582679204
Cited by
21
References
4
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 1
FWCI
0.79
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/misc/userlicense.xhtml (vor)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense (W81XWH-09-1-0392, W81XWH-09-1-0402)
  • HHS | NIH | National Institute on Drug Abuse (DA010044, R01DA014133)
  • HHS | NIH | National Institute of Mental Health (MH090963)
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (NS34696)
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 › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
WAVE1, dopamine D1 receptor, cocaine, cocaine sensitization, cocaine withdrawal, Arp2/3 complex, actin polymerization, Cdk5 phosphorylation, dendritic spine density, medium spiny neurons, nucleus accumbens, glutamatergic synapses, NMDA receptor, place preference, striatum
MeSH terms
Animals, Cocaine, Mice, Transgenic, Motor Activity, Neurons, Nucleus Accumbens, Phosphorylation, Spatial Behavior, Receptors, N-Methyl-D-Aspartate, Receptors, Dopamine D1, Mice, Knockout, Dopamine Uptake Inhibitors, Excitatory Postsynaptic Potentials, Wiskott-Aldrich Syndrome Protein Family, Electrophysiological Phenomena

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