AMPA-receptor involvement in c-fos expression in the medial prefrontal cortex and amygdala dissociates neural substrates of conditioned activity and conditioned reward

Eur J Neurosci. 1999 Nov;11(11):4089-98. doi: 10.1046/j.1460-9568.1999.00828.x.


Exposure to an environment, previously conditioned to amphetamine (1 mg/kg, i.p.), induced locomotor activity and c-fos expression (a marker for neuronal activation) in the mouse medial prefrontal cortex (mPFC) and amygdala; acute or repeated amphetamine (1 mg/kg, i.p.) administration induced c-fos expression additionally in the nucleus accumbens. An alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-receptor antagonist, 2, 3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinoxaline (NBQX), blocked expression of conditioned activity, and prevented the increase in c-fos expression in mPFC, implicating mPFC AMPAergic transmission in the conditioned component of behavioural sensitization to amphetamine. NBQX failed to block the expression of amphetamine-conditioned place preference, a measure of conditioned reward, or conditioned c-fos expression in the amygdala, an area implicated in the expression of conditioned place preference. These findings indicate that the conditioned components of behavioural sensitization depend on AMPA-receptor-mediated activation in mPFC, but that conditioned reward does not.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Choice Behavior / drug effects
  • Choice Behavior / physiology*
  • Conditioning, Operant / physiology*
  • Dextroamphetamine / pharmacology*
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Neurons / physiology*
  • Nucleus Accumbens / physiology
  • Prefrontal Cortex / physiology*
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-fos / genetics*
  • Quinoxalines / pharmacology*
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / physiology*
  • Reward


  • Proto-Oncogene Proteins c-fos
  • Quinoxalines
  • Receptors, AMPA
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Dextroamphetamine