The role of glutamate receptor redistribution in locomotor sensitization to cocaine

Carrie R. Ferrario, Xuan Li, Xiaoting Wang, Jeremy M. Reimers, Jamie L. Uejima, Marina E. Wolf

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

α-Amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) surface expression in the nucleus accumbens (NAc) is enhanced after withdrawal from repeated cocaine exposure. However, it is unclear whether this contributes to the expression of locomotor sensitization and whether similar changes can be observed in other striatal regions. In this study we examined the relationship between AMPAR surface expression in the NAc and locomotor sensitization. We also examined AMPAR distribution in the dorsolateral striatum (DS) and NMDA receptor (NMDAR) distribution in the NAc and DS. Trends but no significant changes in NMDAR distribution were found in the NAc after withdrawal. No NMDAR changes were observed in the DS. AMPAR surface expression was increased in the NAc 15 days after the last exposure to cocaine, but decreased in the DS. Re-exposure to cocaine on withdrawal day 14 decreased AMPAR surface expression in the NAc 24 h, but not 30 min, after challenge, but increased it in the DS 24 h and 30 min after challenge. Locomotor sensitization was evaluated at times associated with increased or decreased AMPAR surface expression in the NAc. The magnitude of sensitization did not vary with changes in the level of AMPAR surface expression, nor was it significantly reduced by decreasing AMPAR transmission through intra-NAc infusion of CNQX before cocaine challenge. On the basis of our results, and other findings, we suggest that the expression of sensitization has no clear relationship to altered AMPAR surface expression in the NAc, although the latter may have a role in the enhanced pursuit and self-administration of drugs observed in sensitized rats.

Original languageEnglish (US)
Pages (from-to)818-833
Number of pages16
JournalNeuropsychopharmacology
Volume35
Issue number3
DOIs
StatePublished - Feb 2010

Keywords

  • AMPA receptor
  • Cocaine
  • Dorsal striatum
  • NMDA receptor
  • Nucleus accumbens
  • Sensitization

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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