N-methyl-D-aspartate mediated responses decrease with age in Fischer 344 rat brain.
N-Methyl-D-aspartate (NMDA) receptor-mediated responses were studied in hippocampus, cortex, and striatum of Fischer 344 rats of various ages (3-5, 12-14, or 24-28 months old; young, middle-aged, and senescent or old, respectively) to determine whether aging alters the function of NMDA receptors. NMDA-induced inhibition of muscarinic-stimulated phosphoinositide hydrolysis in hippocampus, and NMDA-stimulated release of [3H]norepinephrine (NE) or [3H]dopamine (DA) were used as indices of NMDA receptor function. The muscarinic agonist carbachol (1 mM) stimulated PI hydrolysis in hippocampi from all three age groups with no significant differences between the groups. NMDA inhibited the carbachol-evoked PI response in a concentration-dependent manner (10-100 microM) in all age groups. However, the NMDA-induced (100 microM) inhibition of the carbachol-stimulated response was markedly reduced in an age-dependent manner with losses of 25% and 53% in middle-aged and senescent rats compared to young. Concentration-effect curves for NMDA-stimulated [3H]NE release were determined using hippocampal and cortical slices from rats of the three age groups. In the hippocampus the maximal response for NMDA was significantly decreased from 6.55 fractional [3H]NE release in young to 4.51 and 4.18 in middle-aged and old rats, respectively, with no age-related changes in the potency of NMDA or slope of the curves. In cortical slices the maximal response was significantly reduced in an age-dependent manner by 23% in the senescent rats compared to the young rats. NMDA-stimulated [3H]DA release from striatal slices was significantly lower in the senescent rats at concentrations of NMDA from 500-2000 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
Institute for Neuroscience, University of Texas, Austin.
R A
RA
Gonzales
L M
LM
Brown
T W
TW
Jones
R D
RD
Trent
S L
SL
Westbrook
S W
SW
Leslie
D000375:Aging / Q000502:physiology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D018377:Neurotransmitter Agents; D010716:Phosphatidylinositols; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D002217:Carbachol; D004298:Dopamine; D009638:Norepinephrine