Premium
Amphetamine potentiates NMDA receptor currents in midbrain dopamine neurons
Author(s) -
Ingram Susan L.,
Li Minghua,
Underhill Suzanne M.,
Amara Susan G.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.885.1
Subject(s) - nmda receptor , ampa receptor , amphetamine , dopamine , chemistry , dopamine transporter , neuroscience , glutamate receptor , pharmacology , ifenprodil , biology , dopaminergic , receptor , biochemistry
Amphetamine (AMPH) is known to increase extracellular concentrations of dopamine and glutamate. AMPH enhances extracellular dopamine primarily by competing with dopamine for the dopamine transporter (DAT); however, it is not known how AMPH alters concentrations of glutamate. Recently, we determined that acute AMPH exposure leads to internalization of the glutamate transporter, EAAT3, in dopamine neurons in a DAT‐dependent manner. Electrophysiological studies determined that AMPA:NMDA ratios are decreased with AMPH superfusion primarily due to potentiation of NMDA responses. NR2B‐selective inhibitors, ifenprodil and Ro25–6981, abolish the AMPH‐induced increase in NMDA currents. Blockade of synaptic NMDA receptors with the use‐dependent NMDA antagonist, MK‐801, blocked basal evoked NMDA currents but did not inhibit AMPH‐and NR2B‐dependent evoked NMDA currents. These results indicate that that new NMDA receptors are activated by AMPH. Further, Group I metabotropic glutamate receptor (mGluR) antagonists also inhibit AMPH potentiation of NMDA currents. Additional studies are focused on determining if NR2B‐containing receptors are activated by synaptic glutamate spillover, recruited to the synapse, or modified by second messenger signaling in midbrain dopamine neurons. Supported by ARRA‐funded NIH grant DA07595 (SGA) and DA024041 (SLI).