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The Journal of Neuroscience, September 24, 2008, 28(39):9670-9681; doi:10.1523/JNEUROSCI.2151-08.2008

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Development/Plasticity/Repair
Region-Specific Changes in the Subcellular Distribution of AMPA Receptor GluR1 Subunit in the Rat Ventral Tegmental Area after Acute or Chronic Morphine Administration

Diane A. Lane,¹ Andree A. Lessard,¹ June Chan,¹ Eric E. O. Colago,¹ Yan Zhou,² Stefan D. Schlussman,² Mary Jeanne Kreek,² and Virginia M. Pickel¹

¹Department of Neurology and Neuroscience, Division of Neurobiology, Weill Medical College of Cornell University, New York, New York 10021, and ²Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10065

Correspondence should be addressed to Dr. Diane A. Lane, Department of Neurology and Neuroscience, Division of Neurobiology, Weill Medical College of Cornell University, 411 East 69th Street, Room 410, New York, NY 10021. Email: dal2021{at}med.cornell.edu

Opiate addiction is characterized by progressive increases in drug intake over time suggesting maladaptive changes in motivational and reward systems. These behaviors are mediated by dopaminergic neurons originating from the ventral tegmental area (VTA), and long-term changes of these dopaminergic neurons are attributed to increased postsynaptic glutamatergic activation. Indeed, chronic morphine administration is known to increase AMPA receptor glutamate receptor 1 (GluR1) subunit in the VTA. However, there is no ultrastructural evidence that morphine affects the expression or surface availability of GluR1 subunits in VTA neurons of defined distribution or transmitter phenotype. Therefore, we examined electron microscopic immunolabeling of GluR1 and tyrosine hydroxylase (TH) in two VTA regions of rats perfused 1 h after a single injection of morphine, or chronic morphine in intermittent-escalating doses for 14 d, and appropriate saline controls. Acute morphine administration produced a significant increase in GluR1 immunogold particles at the plasma membrane and postsynaptic densities in both TH- and non-TH-containing dendrites in the parabrachial VTA, a region that contains mainly prefrontal-cortical-projecting dopaminergic neurons involved in motivation and drug-seeking behavior. Chronic morphine administration maintained the increased synaptic GluR1 labeling in the parabrachial VTA, but also increased the number of GluR1-labeled synapses and TH immunoreactivity in dendrites of the paranigral VTA where substantially more dopaminergic neurons project to limbic structures implicated in locomotor activation and reward. These results demonstrate a region- and dose-dependent redistribution of GluR1-containing AMPA receptors, which is consistent with acute morphine activation of cortical-projecting VTA neurons and chronic morphine activation of limbic-projecting VTA neurons.

Key words: synaptic plasticity; dopamine; tyrosine hydroxylase; ultrastructure; multivesicular bodies; reward

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Received May 12, 2008; revised Aug. 13, 2008; accepted Aug. 15, 2008.

Correspondence should be addressed to Dr. Diane A. Lane, Department of Neurology and Neuroscience, Division of Neurobiology, Weill Medical College of Cornell University, 411 East 69th Street, Room 410, New York, NY 10021. Email: dal2021{at}med.cornell.edu

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