Clozapine induction of ERK1/2 cell signalling via the EGF receptor in mouse prefrontal cortex and striatum is distinct from other antipsychotic drugs
Avril Pereira, Anthony Sugiharto-Winarno, Betty Zhang, Peter Malcolm, George Fink, Suresh Sundram
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY | CAMBRIDGE UNIV PRESS | Published : 2012
Treatment resistance remains a major obstacle in schizophrenia, with antipsychotic drugs (APDs) being ineffective in about one third of cases. Poor response to standard therapy leaves the APD clozapine as the only effective treatment for many patients. The reason for the superior efficacy of clozapine is unknown, but as we have proposed previously it may involve modulation of neuroplasticity and connectivity through induction of interconnected mitogenic signalling pathways. These include the mitogen-activated protein kinase-extracellular signal regulated kinase (MAPK-ERK) cascade and epidermal growth factor (EGF)/ErbB systems. Clozapine, distinct from other APDs, induced initial inhibition a..View full abstract
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Awarded by NHMRC
We thank the NHMRC (Project grant 628802); One-in-Five Assoc. Inc. and the Woods Family Research Program for grants-in-aid of this research and the Victorian State Government for Operational Infrastructure Support. We also thank Bristol-Myers Squibb and Eli Lilly for their generous gifts of aripiprazole and olanzapine, respectively.