TY - JOUR
T1 - Effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor blockade on increased cerebral O2 consumption in Eker rats
AU - Weiss, Harvey R.
AU - Liu, Xia
AU - Hunter, Christine
AU - Z.Chi, Oak
N1 - Funding Information: This work was supported, in part, by a grant from the New Jersey Governor's Council on Autism .
PY - 2009/10/6
Y1 - 2009/10/6
N2 - 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 (4 weeks) male control Long Evans (N = 14) and Eker (N = 14) rats (70-100 g) were divided into control and NBQX (50 mg/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.
AB - 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 (4 weeks) male control Long Evans (N = 14) and Eker (N = 14) rats (70-100 g) were divided into control and NBQX (50 mg/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.
KW - Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
KW - Cerebral O consumption
KW - Cerebral blood flow
KW - Excitatory amino acid
KW - Rat
KW - Tuberous sclerosis
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U2 - https://doi.org/10.1016/j.brainres.2009.08.022
DO - https://doi.org/10.1016/j.brainres.2009.08.022
M3 - Article
C2 - 19686708
SN - 0006-8993
VL - 1294
SP - 138
EP - 143
JO - Brain Research
JF - Brain Research
ER -