Calcium-permeable AMPA receptors are present in nucleus accumbens synapses after prolonged withdrawal from cocaine self-administration but not experimenter-administered cocaine

James E. McCutcheon, Xiaoting Wang, Kuei Y. Tseng, Marina Wolf, Michela Marinelli

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Repeated noncontingent cocaine injections, which lead to behavioral sensitization, increase AMPA receptor (AMPAR) transmission in the rodent nucleus accumbens (NAc) in a withdrawal-dependent manner. On withdrawal days (WD) 10-21, this is attributable to upregulation of GluA1A2-containing AMPARs. However, synaptic incorporation of GluA2-lacking/Ca2+-permeable AMPARs (CP-AMPARs) was observed after longer withdrawal (WD35) from repeated noncontingent cocaine injections in young mice (Mameli et al., 2009). CP-AMPARs had previously been observed in NAc synapses only after prolonged (WD30-WD47) withdrawal from extended-access cocaine self-administration. Our goal was to determine whether rats receiving repeated noncontingent cocaine injections during adulthood similarly exhibit CP-AMPARs in the NAc after prolonged withdrawal. For comparison, we began by evaluating CP-AMPARs on WD35-WD49 after extended-access cocaine self-administration. Confirming our previous results, whole-cell recordings revealed inwardly rectifying AMPAR EPSCs, a hallmark of CP-AMPARs. This was observed in both core and shell. Next, we conducted the same analysis in adult rats treated with eight daily noncontingent cocaine injections and recorded on WD35-WD49. AMPAR EPSCs in core and shell did not show inward rectification and were insensitive to 1-naphthylacetylspermine (a selective antagonist of CP-AMPARs). Locomotor sensitization could still be demonstrated after this long withdrawal period, although the upregulation of GluA1A2-containing AMPARs observed at earlier withdrawaltimes was no longer detected. In conclusion, in adult rats, accumulation of synaptic CP-AMPARs in the NAc occurs after prolonged withdrawal from extended-access cocaine self-administration but not after prolonged withdrawal from noncontingent cocaine injections.

Original languageEnglish (US)
Pages (from-to)5737-5743
Number of pages7
JournalJournal of Neuroscience
Volume31
Issue number15
DOIs
StatePublished - Apr 13 2011
Externally publishedYes

Fingerprint

Self Administration
AMPA Receptors
Nucleus Accumbens
Cocaine
Synapses
Calcium
Injections
Up-Regulation
Patch-Clamp Techniques
Rodentia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Calcium-permeable AMPA receptors are present in nucleus accumbens synapses after prolonged withdrawal from cocaine self-administration but not experimenter-administered cocaine. / McCutcheon, James E.; Wang, Xiaoting; Tseng, Kuei Y.; Wolf, Marina; Marinelli, Michela.

In: Journal of Neuroscience, Vol. 31, No. 15, 13.04.2011, p. 5737-5743.

Research output: Contribution to journalArticle

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abstract = "Repeated noncontingent cocaine injections, which lead to behavioral sensitization, increase AMPA receptor (AMPAR) transmission in the rodent nucleus accumbens (NAc) in a withdrawal-dependent manner. On withdrawal days (WD) 10-21, this is attributable to upregulation of GluA1A2-containing AMPARs. However, synaptic incorporation of GluA2-lacking/Ca2+-permeable AMPARs (CP-AMPARs) was observed after longer withdrawal (WD35) from repeated noncontingent cocaine injections in young mice (Mameli et al., 2009). CP-AMPARs had previously been observed in NAc synapses only after prolonged (WD30-WD47) withdrawal from extended-access cocaine self-administration. Our goal was to determine whether rats receiving repeated noncontingent cocaine injections during adulthood similarly exhibit CP-AMPARs in the NAc after prolonged withdrawal. For comparison, we began by evaluating CP-AMPARs on WD35-WD49 after extended-access cocaine self-administration. Confirming our previous results, whole-cell recordings revealed inwardly rectifying AMPAR EPSCs, a hallmark of CP-AMPARs. This was observed in both core and shell. Next, we conducted the same analysis in adult rats treated with eight daily noncontingent cocaine injections and recorded on WD35-WD49. AMPAR EPSCs in core and shell did not show inward rectification and were insensitive to 1-naphthylacetylspermine (a selective antagonist of CP-AMPARs). Locomotor sensitization could still be demonstrated after this long withdrawal period, although the upregulation of GluA1A2-containing AMPARs observed at earlier withdrawaltimes was no longer detected. In conclusion, in adult rats, accumulation of synaptic CP-AMPARs in the NAc occurs after prolonged withdrawal from extended-access cocaine self-administration but not after prolonged withdrawal from noncontingent cocaine injections.",
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