Reduced bicuculline response and GABAA agonist binding in aged rat hippocampus.
Extracellular field recordings from CA1 pyramidal cells in the rat hippocampal slice preparation were used to examine the effects of age on gamma-aminobutyric acid (GABA)-mediated recurrent inhibition. The actions of bicuculline (1-100 microM), a GABAA antagonist, were assessed in slices from young (1-3 months) and aged (26 months) Fischer 344 rats. Pre-drug population spike amplitudes were smaller in slices from aged rats. Bicuculline increased population spike amplitudes in slices from both age groups, but slices from young rats were more sensitive to the antagonist. Bicuculline also produced multiple population spikes in slices from both age groups, however the increase in population spike burst durations was much greater in slices from young rats than in slices from aged rats. Agonist radiolabeled GABAA binding site density was significantly decreased in hippocampal tissue from aged rats. Our results suggest there is a reduction in GABAergic inhibition in hippocampal slices from aged rats, possibly mediated by a decrease in GABAA receptors.
Post-Munson
D J
DJ
Bristol-Myers Squibb Pharmaceutical Research Institute, Department of CNS/Biophysics & Molecular Biology, Wallingford, CT 06492.
Lum-Ragan
J T
JT
Mahle
C D
CD
Gribkoff
V K
VK
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001640:Bicuculline / Q000493:pharmacokinetics / Q000494:pharmacology*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D009118:Muscimol / Q000493:pharmacokinetics; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000378:metabolism
D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D001640:Bicuculline