Reduced effect of stimulation of AMPA receptors on cerebral O2 consumption in a rat model of autism

Harvey R. Weiss, Xia Liu, Parneet Grewal, Oak Z. Chi

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Previous work demonstrated that basal alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid (AMPA) receptor activity did not contribute to the elevated regional cerebral O2 consumption in the brains of Eker rat (an autism-tuberous sclerosis model). We tested the hypothesis that increased stimulation of AMPA receptors also would not augment cerebral O2 consumption in the Eker rat. Three cortical sites were prepared for administration of saline, 10-4 and 10-3 M AMPA in young (4 weeks) male control Long Evans and Eker rats (70-100 g). Cerebral blood flow (14C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. Receptor levels were studied through Western analysis of the GLuR1 subunit of the AMPA receptor. We found significantly increased cortical O2 consumption (+33%) after 10-4 M AMPA in control rats. The higher dose of AMPA did not further increase consumption. In the Eker rats, neither dose led to a significant increase in cortical O2 consumption. Regional blood flow followed a similar pattern to oxygen consumption but cortical O 2 extraction did not differ. Cortical AMPA receptor protein levels were significantly reduced (-21%) in the Eker compared to control rats. Both O2 consumption and blood flow were significantly elevated in the pons of the Eker rats compared to control. These data demonstrate a reduced importance of AMPA receptors in the control of cortical metabolism, related to reduced AMPA receptor protein, in the Eker rat. This suggests that increasing AMPA receptor activity may not be an effective treatment for children with autism spectrum disorders as they also have reduced AMPA receptor number.

Original languageEnglish (US)
Pages (from-to)837-841
Number of pages5
JournalNeuropharmacology
Volume63
Issue number5
DOIs
StatePublished - Oct 2012

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Keywords

  • Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
  • Autism spectrum disorders
  • Cerebral O consumption
  • Cerebral blood flow
  • Excitatory amino acids
  • Rats

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