The non-receptor tyrosine kinase Pyk2 modulates acute locomotor effects of cocaine in D1 receptor-expressing neurons of the nucleus accumbens

Benoit de Pins, Enrica Montalban, Peter Vanhoutte, Albert Giralt, Jean Antoine Girault

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8 Scopus citations


The striatum is critical for cocaine-induced locomotor responses. Although the role of D1 receptor-expressing neurons is established, underlying molecular pathways are not fully understood. We studied the role of Pyk2, a non-receptor, calcium-dependent protein-tyrosine kinase. The locomotor coordination and basal activity of Pyk2 knock-out mice were not altered and major striatal protein markers were normal. Cocaine injection increased Pyk2 tyrosine phosphorylation in mouse striatum. Pyk2-deficient mice displayed decreased locomotor response to acute cocaine injection. In contrast, locomotor sensitization and conditioned place preference were normal. Cocaine-activated ERK phosphorylation, a signaling pathway essential for these late responses, was unaltered. Conditional deletion of Pyk2 in the nucleus accumbens or in D1 neurons reproduced decreased locomotor response to cocaine, whereas deletion of Pyk2 in the dorsal striatum or in A2A receptor-expressing neurons did not. In mice lacking Pyk2 in D1-neurons locomotor response to D1 agonist SKF-81297, but not to an anticholinergic drug, was blunted. Our results identify Pyk2 as a regulator of acute locomotor responses to psychostimulants. They highlight the role of tyrosine phosphorylation pathways in striatal neurons and suggest that changes in Pyk2 expression or activation may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine action.
Original languageEnglish (US)
JournalScientific Reports
Issue number1
StatePublished - Apr 20 2020
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2022-06-14
Acknowledgements: BdP was supported by the Fondation pour la Recherche Médicale (FRM, FDT201805005390). AG is a Ramón y Cajal fellow (RYC-2016-19466) supported by a grant from Ministerio de Ciencia, Innovación y Universidades (RTI2018-094678-A-I00). PV lab was supported by CNRS, Inserm, Sorbonne University, FRM, Agence Nationale de la Recherche (ANR-PRCI-15-CE16-001 and PRC-18-CE37-003-02) and the Bio-Psy cluster of excellence. JAG lab was supported by Inserm, Sorbonne University, FRM, ERC AdG-2009, a KAUST collaborative grant to JAG and S Arold, ANR-19-CE16-0020, and Bio-Psy (Biology for Psychiatry) cluster of excellence (Investissements d’Avenir, ANR-11-IDEX-0004-02). Relevant experiments were carried out at the IFM Rodent breeding and phenotyping facility and the IFM Cell and Tissue Imaging facility. The IFM Cell and Tissue Imaging facility benefited from supports of Espoir en Tête/Fondation pour la Recherche sur le Cerveau (FRC), Région Ile-de-France, and Inserm. The authors thank the late Paul Greengard (The Rockefeller University) for the gift of antibodies for synapsin 1 and DARPP-32, and Alban de Kerchove d’Exaerde (Brussels Free University) for providing Adora2a
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

ASJC Scopus subject areas

  • General


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