Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse

Idit Golani, Hagar Tadmor, Andres Buonanno, Ilana Kremer, Alon Shamir

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia. Herein we characterized the behavioral profile and molecular changes resulting from pharmacologically blocking the ErbB signaling pathway during a critical period in the development of decision making, planning, judgments, emotions, social cognition and cognitive skills, namely adolescence. We demonstrate that chronic administration of the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ) to adolescent mice elevated striatal dopamine levels and reduced preference for sucrose without affecting locomotor activity and exploratory behavior. In adulthood, adolescent JNJ-treated mice continue to consume less sucrose and needed significantly more correct-response trials to reach the learning criterion during the discrimination phase of the T-maze reversal learning task than their saline-injected controls. In addition, JNJ mice exhibited deficit in reference memory but not in working memory as measured in the radial arm maze. Inhibition of the pathway during adolescence did not affect exploratory behavior and locomotor activity in the open field, social interaction, social memory, and reversal learning in adult mice. Our data suggest that alteration of ErbB signaling during adolescence resulted in changes in the dopaminergic systems that emerge in pathological learning and hedonic behavior in adulthood, and pinpoints the possible role of the pathway in the development of cognitive skills and motivated behavior.

Original languageEnglish
Pages (from-to)1808-1818
Number of pages11
JournalEuropean Neuropsychopharmacology
Issue number11
StatePublished - 1 Nov 2014

Bibliographical note

Publisher Copyright:
© 2014 Elsevier B.V. and ECNP.


This work was supported by the National Institute of Psychobiology Young Investigator Research ( 218-12-13 ) Grant to A.S. and by the Technion V.P.R. Fund for Medical Research ( 1011359 ; A.S.). We are also grateful for the financial support from Ort Bruda College (I.G.).

FundersFunder number
National Institute of Psychobiology218-12-13
Ort Bruda College
National Institute of Child Health and Human DevelopmentZIAHD000711
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Technion-Israel Institute of Technology1011359


    • Animal behavior
    • Cognition
    • Dopaminergic system
    • ErbB receptor
    • Neuregulin
    • Schizophrenia


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