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 Wolf

Research output: Contribution to journalArticle

62 Citations (Scopus)

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 1 2010
Externally publishedYes

Fingerprint

Propionates
Nucleus Accumbens
Glutamate Receptors
Cocaine
N-Methyl-D-Aspartate Receptors
6-Cyano-7-nitroquinoxaline-2,3-dione
bucide
Corpus Striatum
Self Administration

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

The role of glutamate receptor redistribution in locomotor sensitization to cocaine. / Ferrario, Carrie R.; Li, Xuan; Wang, Xiaoting; Reimers, Jeremy M.; Uejima, Jamie L.; Wolf, Marina.

In: Neuropsychopharmacology, Vol. 35, No. 3, 01.02.2010, p. 818-833.

Research output: Contribution to journalArticle

Ferrario, Carrie R. ; Li, Xuan ; Wang, Xiaoting ; Reimers, Jeremy M. ; Uejima, Jamie L. ; Wolf, Marina. / The role of glutamate receptor redistribution in locomotor sensitization to cocaine. In: Neuropsychopharmacology. 2010 ; Vol. 35, No. 3. pp. 818-833.
@article{98b80e8dbc314f088662f8b6a9ed7012,
title = "The role of glutamate receptor redistribution in locomotor sensitization to cocaine",
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.",
keywords = "AMPA receptor, Cocaine, Dorsal striatum, NMDA receptor, Nucleus accumbens, Sensitization",
author = "Ferrario, {Carrie R.} and Xuan Li and Xiaoting Wang and Reimers, {Jeremy M.} and Uejima, {Jamie L.} and Marina Wolf",
year = "2010",
month = "2",
day = "1",
doi = "10.1038/npp.2009.190",
language = "English (US)",
volume = "35",
pages = "818--833",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - The role of glutamate receptor redistribution in locomotor sensitization to cocaine

AU - Ferrario, Carrie R.

AU - Li, Xuan

AU - Wang, Xiaoting

AU - Reimers, Jeremy M.

AU - Uejima, Jamie L.

AU - Wolf, Marina

PY - 2010/2/1

Y1 - 2010/2/1

N2 - 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.

AB - 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.

KW - AMPA receptor

KW - Cocaine

KW - Dorsal striatum

KW - NMDA receptor

KW - Nucleus accumbens

KW - Sensitization

UR - http://www.scopus.com/inward/record.url?scp=75749129365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75749129365&partnerID=8YFLogxK

U2 - 10.1038/npp.2009.190

DO - 10.1038/npp.2009.190

M3 - Article

C2 - 19924109

AN - SCOPUS:75749129365

VL - 35

SP - 818

EP - 833

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 3

ER -