Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus accumbens

Amy C. Boudreau, Marina Wolf

Research output: Contribution to journalArticle

351 Citations (Scopus)

Abstract

Regulation of AMPA receptor trafficking is important for many forms of neuronal plasticity. In this study, a protein cross-linking assay was used to evaluate the contribution of AMPA receptor trafficking to plasticity associated with behavioral sensitization, an animal model of drug addiction. Cross-linking was used to distinguish between cell surface and intracellular AMPA receptors in nucleus accumbens (NAc) tissue obtained from rats treated repeatedly with saline or cocaine. Surface/intracellular (S/I) ratios for glutamate receptor 1 (GluR1) and GluR2/3 subunits were increased 21 d after the last injection in cocaine-sensitized rats but not rats that failed to sensitize, and the magnitude of the S/I ratio for cocaine-sensitized rats was positively correlated with the magnitude of behavioral sensitization. At the 1 d withdrawal time, cocaine did not alter S/I ratios, and there was no correlation between S/I ratios and behavioral sensitization. The majority of surface-expressed GluR1 detected with this assay was associated with synapses, based on coimmunoprecipitation with postsynaptic density protein of 95 kDa. These findings suggest that behavioral sensitization to cocaine is associated with a slowly developing redistribution of AMPA receptors to the surface of NAc neurons. Motor execution of drug-seeking responses depends on activation of AMPA receptors on NAc neurons by glutamate afferents originating in cortical and limbic regions. We propose that drug-seeking responses are more effectively triggered in cocaine-sensitized rats because of increased cell surface expression of AMPA receptors.

Original languageEnglish (US)
Pages (from-to)9144-9151
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number40
DOIs
StatePublished - Oct 5 2005
Externally publishedYes

Fingerprint

AMPA Receptors
Nucleus Accumbens
Cocaine
Glutamate Receptors
Afferent Neurons
Neuronal Plasticity
Pharmaceutical Preparations
Synapses
Substance-Related Disorders
Glutamic Acid
Animal Models
Neurons
Injections
Proteins

Keywords

  • Addiction
  • AMPA receptor
  • Cocaine
  • Nucleus accumbens
  • Rat
  • Sensitization
  • Trafficking
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus accumbens. / Boudreau, Amy C.; Wolf, Marina.

In: Journal of Neuroscience, Vol. 25, No. 40, 05.10.2005, p. 9144-9151.

Research output: Contribution to journalArticle

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