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

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 O₂ 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.