PKD1-mediated phosphorylation at dopamine D2 receptor serine 365 site in dorsal striatum underlies cocaine-induced locomotor hyperactivity.

Xinyu Zhang, Ziran Zhang, Ying Wang, Linlin Sun, Ning Wang

Abstract read

In one paragraph

Article in IBRO neuroscience reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

5 authors.

Xinyu ZhangDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.

Ziran ZhangDepartment of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Ying WangDepartment of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Linlin SunDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.

Ning WangDepartment of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Locomotor hyperactivity is an early behavioural adaptation in cocaine use disorder, driven by increased dopamine levels in the striatum. The expression, sensitivity, and availability of dopamine D2 receptor (D2R) are significantly associated with cocaine use disorder. However, neither D2R agonists nor antagonists are optimal for clinical intervention because of their side effects. Therefore, targeting regulatory proteins that can effectively disrupt cocaine-induced D2R malfunction may offer improved strategies for cocaine use disorder. Here, we report that knockdown of protein kinase D1 (PKD1) in the rat dorsal striatum attenuates cocaine-induced locomotor hyperactivity. PKD1 phosphorylates the serine 365 site (S365) of D2R, reduces its surface localisation, and enhances downstream extracellular signal-regulated kinase (ERK) signalling. Tat-S365, an engineered Tat fusion-peptide blocked S365 phosphorylation in D2R, thereby decreasing the pERK levels.

Indexed as

Cocaine use disorderDopamine D2 receptorLocomotor activityPeptideProtein kinase D1

Identifiers

PMID40606639

DOI10.1016/j.ibneur.2025.06.013

PMCPMC12221609

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.