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Aging‐Associated Changes in the Pharmacological Properties of the Benzodiazepine (ω) Receptor Isotypes in the Rat Hippocampus
Author(s) -
Ruano Diego,
Benavides Jesus,
Machado Alberto,
Vitorica Javier
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64020867.x
Subject(s) - hippocampus , benzodiazepine , neuroscience , receptor , gabaa receptor , biology , pharmacology , medicine
The aging‐associated changes in hippocampal benzodiazepine (ω) receptor isotypes have been investigated in rats of the Wistar and Fischer 344 strains. Displacement experiments of [ 3 H]flunitrazepam binding by zolpidem demonstrated that in hippocampal membranes from adult (3‐month‐old) Wistar strain rats, high (type I; ω 1 )‐, intermediate (type II M ; ω 2 )‐, and low (type II L ; ω 5 )‐ affinity sites for this imidazopyridine account for 27.1 ± 7.5, 44.2 ± 7.5, and 28.8 ± 5.1%, respectively. In hippocampal membranes from aged (24‐month‐old) rats of the same strain, the relative abundance of these sites was 42.8 ± 9.3, 26.3 ± 4, and 36.0 ± 5.9%, respectively. In contrast, no significant difference was observed in the whole benzodiazepine (ω) binding site density between adult and aged rats. The increase in type I (ω 1 ) binding site density in the hippocampus of aged rats was also demonstrated in saturation experiments with [ 3 H]zolpidem. This aging‐induced increase in [ 3 H]zolpidem binding was also observed in hippocampal membranes from Fischer 344 rats. Moreover, in both rat strains, GABA induced a greater enhancement of [ 3 H]zolpidem (5 n M ) binding to type I (ω 1 ) sites (GABA shift) in aged than in adult hippocampal membranes. Quantitative autoradiographic analysis of [ 3 H]zolpidem binding to coronal brain sections from adult and aged Fischer 344 rats demonstrated that the aging‐associated increases in the density of type I (ω 1 ) binding sites were restricted to the hippocampus. Moreover, increases in binding density were larger in the dentate gyrus and in the CA2 field than in the CA1 and CA3 fields.