TY - JOUR T1 - Increased insertion of GluR2-lacking AMPA receptors at hippocampal synapses upon repeated morphine administration JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.109.060301 SP - mol.109.060301 AU - Sophie K Billa AU - Jie Liu AU - Nicole L Bjorklund AU - Namita Sinha AU - Yu Fu AU - Patricia Shinnick-Gallagher AU - Jose A Moron Y1 - 2010/02/16 UR - http://molpharm.aspetjournals.org/content/early/2010/02/16/mol.109.060301.abstract N2 - Evidence suggests that the long-term adaptations in the hippocampus after repeated drug treatment may parallel its role during memory formation. The neuroplasticity which subserves learning and memory is also thought to underlie addictive processes. We have previously reported 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 thought 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 2 (GluR2) 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 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 (LTD) 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.The American Society for Pharmacology and Experimental Therapeutics ER -