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Altered prelimbic cortex output during cue-elicited drug seeking

Academic Article
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Overview

authors

  • Miller, Courtney
  • Marshall, J. F.

publication date

  • August 2004

journal

  • Journal of Neuroscience  Journal

abstract

  • Cocaine treatment paired with environmental cues establishes a conditioned place preference (CPP) for that environment. After expression of this preference, rats show elevated levels of immediate early genes (IEGs; e.g. c-fos) in the prelimbic cortex (PrL), basolateral amygdala complex (BLC), and nucleus accumbens core (NAcc) compared with drug-unpaired controls. These findings, together with the known connections between these regions, suggest that they function as a circuit contributing to cue-elicited craving. To investigate the function of this circuit during drug-seeking, we characterized Fos immunoreactivity of particular neuron classes in each region. To distinguish between IEG activation of GABAergic and non-GABAergic (principally, excitatory projection) neurons, we combined Fos immunohistochemistry with immunohistochemistry for glutamic acid decarboxylase 67 (GAD67) or calcium/calmodulin-dependent protein kinase II (CAMKII) proteins. Within the BLC and NAcc of drug-paired and drug-unpaired animals tested for CPP, we observed no significant differences in the percentage of Fos-immunoreactive (IR) cells that were also GAD67-IR. We also observed no group difference in the degree of Fos/CAMKII overlap in the BLC. However, in PrL, the degree of Fos/GAD67 overlap in the drug-paired group was significantly higher than in the drug-unpaired group. Also, the Fos/CAMKII overlap in the entire PrL as well as just its layer V was significantly lower in the drug-paired animals compared with controls. These findings suggest that, during CPP expression in cocaine-paired animals, the PrL GABAergic interneurons are preferentially activated while PrL output is attenuated, perhaps through greater inhibition of layer V pyramidal neurons. These results suggest a shifting prefrontal cortex cell population response during cocaine-seeking.

subject areas

  • Amygdala
  • Animals
  • Brain
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cerebral Cortex
  • Cocaine-Related Disorders
  • Cues
  • Glutamate Decarboxylase
  • Immunohistochemistry
  • Isoenzymes
  • Male
  • Nucleus Accumbens
  • Proto-Oncogene Proteins c-fos
  • Rats
  • Rats, Sprague-Dawley
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Research

keywords

  • basolateral amygdala
  • c-Fos
  • cocaine
  • conditioned place preference
  • immediate early gene
  • nucleus accumbens
  • prelimbic cortex
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Identity

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.1685-04.2004

PubMed ID

  • 15295023
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Additional Document Info

start page

  • 6889

end page

  • 6897

volume

  • 24

issue

  • 31

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