Fos and glutamate AMPA receptor subunit coexpression associated with cue-elicited cocaine-seeking behavior in abstinent rats

A. R. Zavala, S. Biswas, R. E. Harlan, Janet Neisewander

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Cocaine-associated cues acquire incentive motivational effects that manifest as craving in humans and cocaine-seeking behavior in rats. We have reported an increase in neuronal activation in rats, measured by Fos protein expression, in various limbic and cortical regions following exposure to cocaine-associated cues. This study examined whether the conditioned neuronal activation involves glutamate AMPA receptors by measuring coexpression of Fos and AMPA glutamate receptor subunits (GluR1, GluR2/3, or GluR4). Rats trained to self-administer cocaine subsequently underwent 22 days of abstinence, during which they were exposed daily to either the self-administration environment with presentations of the light/tone cues previously paired with cocaine infusions (Extinction group) or an alternate environment (No Extinction group). All rats were then tested for cocaine-seeking behavior (i.e. responses without cocaine reinforcement) and Fos and AMPA glutamate receptor subunits were measured postmortem using immunocytochemistry. The No Extinction group exhibited increases in cocaine-seeking behavior and Fos expression in limbic and cortical regions relative to the Extinction group. A large number of Fos immunoreactive cells coexpressed GluR1, GluR2/3, and GluR4, suggesting that an action of glutamate at AMPA receptors may in part drive cue-elicited Fos expression. Importantly, there was an increase in the percentage of cells colabeled with Fos and GluR1 in the anterior cingulate and nucleus accumbens shell and cells colabeled with Fos and GluR4 in the infralimbic cortex, suggesting that within these regions, a greater, and perhaps even different, population of AMPA receptor subunit-expressing neurons is activated in rats engaged in cocaine-seeking behavior.

Original languageEnglish (US)
Pages (from-to)438-452
Number of pages15
JournalNeuroscience
Volume145
Issue number2
DOIs
StatePublished - Mar 16 2007

Fingerprint

AMPA Receptors
Glutamate Receptors
Cocaine
Cues
Self Administration
Gyrus Cinguli
Nucleus Accumbens
Motivation
Glutamic Acid
Immunohistochemistry
Neurons
Light
Psychological Extinction

Keywords

  • c-fos
  • drug conditioning
  • immediate early gene
  • incentive motivation
  • reinstatement

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Fos and glutamate AMPA receptor subunit coexpression associated with cue-elicited cocaine-seeking behavior in abstinent rats. / Zavala, A. R.; Biswas, S.; Harlan, R. E.; Neisewander, Janet.

In: Neuroscience, Vol. 145, No. 2, 16.03.2007, p. 438-452.

Research output: Contribution to journalArticle

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