Behavioral sensitization to cocaine is associated with increased glutamate receptor trafficking to the postsynaptic density after extended withdrawal period

• Published in: Neuroscience 2009-03, Vol.159 (1), p.414-426
• Main Authors: Ghasemzadeh, M.B, Mueller, C, Vasudevan, P
• Format: Article
• Language: English
• Subjects: Actins - metabolism; addiction; AMPA; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Carrier Proteins - metabolism; Cocaine - administration & dosage; Cocaine-Related Disorders - metabolism; Cocaine-Related Disorders - pathology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - ultrastructure; Disks Large Homolog 4 Protein; Dopamine Uptake Inhibitors - administration & dosage; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Homer Scaffolding Proteins; Intracellular Signaling Peptides and Proteins - metabolism; Male; Medical sciences; Membrane Proteins - metabolism; mGluR5; Neurology; Neuropharmacology; NMDA; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Nucleus Accumbens - ultrastructure; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, Glutamate - classification; Receptors, Glutamate - metabolism; scaffolding proteins; Substance Withdrawal Syndrome - metabolism; Substance Withdrawal Syndrome - pathology; synaptic plasticity; Synaptosomes - drug effects; Synaptosomes - metabolism; Time Factors; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism; Ventral Tegmental Area - ultrastructure; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.10.027

Abstract Glutamatergic signaling plays an important role in the behavioral and molecular plasticity observed in behavioral sensitization to cocaine. Redistribution of the glutamate receptors in the synaptosomal membrane fraction was investigated in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area at 1 or 21 days of withdrawal in behaviorally sensitized rats. At 1 day of withdrawal, there were no changes in either tissue level or redistribution of glutamate receptors in nucleus accumbens core and shell and ventral tegmental area. At 21 days of withdrawal, there was a decrease in the expression of mGluR2/3 protein in core and shell, an increase in GluR1 and a decrease in Homer1b/c proteins in the nucleus accumbens core tissue. In dorsolateral striatum, the tissue level of NMDAR2B protein was increased. Moreover, there was an augmented presence of AMPA (GluR1, GluR2), NMDA (NMDAR1, 2A, 2B), and group 1 metabotropic glutamate receptor (mGluR5) proteins in the synaptosomal fraction in core and shell of the nucleus accumbens. There was also an increase in synaptosomal mGluR2/3 protein in nucleus accumbens core. The redistribution of glutamate receptors was selective for nucleus accumbens since no changes were observed in the dorsolateral striatum and ventral tegmental area. While the tissue level of the Homer1b/c protein was selectively reduced in nucleus accumbens core, that of PSD95, PICK1, and actin was not changed in any of the brain regions examined. However, the synaptosomal membrane fraction level of Homer1b/c and PSD95 was increased in nucleus accumbens core and shell, with no changes in PICK1, and a decrease in actin protein. These observations suggest that significant redistribution of glutamate receptors and postsynaptic scaffolding proteins into synaptosomal membrane fraction is associated with withdrawal from behavioral sensitization to cocaine.