RT Journal Article
SR Electronic
T1 Increased Insertion of Glutamate Receptor 2-Lacking α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptors at Hippocampal Synapses upon Repeated Morphine Administration
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 874
OP 883
DO 10.1124/mol.109.060301
VO 77
IS 5
A1 Sophie K. Billa
A1 Jie Liu
A1 Nicole L. Bjorklund
A1 Namita Sinha
A1 Yu Fu
A1 Patricia Shinnick-Gallagher
A1 Jose A. Morón
YR 2010
UL http://molpharm.aspetjournals.org/content/77/5/874.abstract
AB Evidence suggests that the long-term adaptations in the hippocampus after repeated drug treatment may parallel its role during memory formation. The neuroplasticity that subserves learning and memory is also believed to underlie addictive processes. We have reported previously that repeated morphine administration alters local distribution of endocytic proteins at hippocampal synapses, which could in turn affect expression of glutamate receptors. Glutamatergic systems, including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), are believed to be involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are only beginning to be understood. The present study further examines the effects of repeated morphine administration on the expression and composition of AMPARs and the functional ramifications. Twelve hours after the last morphine injection, we observed an increased expression of AMPARs lacking glutamate receptor (GluR) 2 in hippocampal synaptic fractions. Immunoblotting studies show that 12 h after morphine treatment, GluR1 subunits are increased at the postsynaptic density (PSD) and at extrasynaptic sites, whereas GluR3 subunits are only increased at the PSD, and they show how this alters receptor subunit composition. In addition, we provide electrophysiological evidence that AMPARs are switched to Ca2+-permeable (GluR2-lacking) at the synapse 12 h after repeated morphine treatment, affecting the magnitude of long-term depression at hippocampal neurons. We propose that morphine-induced changes in glutamatergic synaptic transmission in the hippocampus may play an important role in the neuroadaptations induced by repeated morphine administration.Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics