Effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor blockade on increased cerebral O(2) consumption in Eker rats.

Previous work had demonstrated that there was elevated regional cerebral O2 consumption in the brains of a tuberous sclerosis model (Eker rat). We tested the hypothesis that the increased cerebral O2 consumption was related to an increased contribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors to the control of cerebral metabolism. Young (4weeks) male control Long Evans (N=14) and Eker (N=14) rats (70-100g) were divided into control and NBQX (50mg/kg, AMPA antagonist) treated animals. Cerebral regional blood flow (14C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. We found significantly increased basal O2 consumption (+85%) in the cortex, hippocampus, cerebellum and pons of the Eker rats. Regional cerebral blood flow was also elevated in Eker rats at baseline (+53%) as was cerebral O2 extraction (+22%). NBQX significantly lowered O2 consumption in all regions of the Long Evans rats (-41%). Cerebral O2 consumption was lowered in the cortex to a lesser extent (-24%) and there were no changes in other regions of the Eker rats after NBQX. Cerebral blood flow was reduced in the Long Evans, but not the Eker rats, after NBQX. In conclusion, Eker rats had significantly elevated cerebral O2 consumption, O2 extraction and blood flow, but this was not related to AMPA receptor activation. In fact, the importance of AMPA receptors in the control of basal cerebral O2 consumption was reduced.