Amphetamine increases phosphorylation of MAPK/ERK at synaptic sites in the rat striatum and medial prefrontal cortex

作者：Mao, Li-Min; Reusch, James M.; Fibuch, Eugene E.; Liu, Zhenguo; Wang, John Q.^*

来源：Brain Research, 2013, 1494: 101-108.

DOI：10.1016/j.brainres.2012.11.038

• Striatum
• Basal ganglia
• Dopamine
• Stimulant
• Postsynaptic density
• Extrasynaptic membrane
• Addiction

Mitogen-activated protein kinases (MAPKs) play a central role in cell signaling. Extracellular signal-regulated kinase (ERIC) is a prototypic subclass of MAPKs and is densely expressed in postmitotic neurons of adult mammalian brains. Active ERIC translocates into the nucleus to regulate gene expression. Additionally, ERIC is visualized in neuronal peripheries, such as distal synaptic structures. While nuclear ERIC is a known sensitive target of psychostimulants, little is known about the responsiveness of synaptic ERIC to stimulants. In this study, we focused on ERIC at synaptic versus extrasynaptic sites and investigated its responses to the psychostimulant amphetamine in the adult rat striatum and medial prefrontal cortex (mPFC) in vivo. We used a pre-validated biochemical fractionation procedure to isolate synapse- and extrasynapse-enriched membranes. We found that two common ERIC isoforms (ERK1 and ERK2) were concentrated more in extrasynaptic fractions than in synaptic fractions in striatal and cortical neurons under normal conditions. At synaptic sites, ERK2 was noticeably more abundant than ERK1. Acute injection of amphetamine induced an increase in ERK2 phosphroylation in the synaptic fraction of striatal neurons, while the drug did not alter extrasynaptic ERK2 phosphorylation. Similar results were observed in the mPFC. In both synaptic and extrasynaptic compartments, total ERK1/2 proteins remained stable in response to amphetamine. Our data establish the subsynaptic distribution pattern of MAPK/ERK in striatal and cortical neurons. Moreover, the synaptic pool of ERK2 in these neurons can be selectively activated by amphetamine.

• 出版日期2013-2-4
• 单位上海交通大学