title: Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.
abstract: Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction.
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Sun
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Quizon
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina, USA. Electronic address: zhuj@sccp.sc.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D001519:Behavior; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D019966:Substance-Related Disorders / Q000235:genetics*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK; dopamine receptor; drug addiction; glutamate receptor; immediate early gene
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