Aging-Associated Changes in the Pharmacological Properties of the Benzodiazepine (ω) Receptor Isotypes in the Rat Hippocampus |
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Authors: | Diego Ruano Jesus Benavides Alberto Machado Javier Vitorica |
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Institution: | Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain;and; Department of Preclinical Research, Synthélabo Recherche (LERS), Bagneux, France |
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Abstract: | Abstract: 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 3H]flunitrazepam binding by zolpidem demonstrated that in hippocampal membranes from adult (3-month-old) Wistar strain rats, high (type I; ω1)-, intermediate (type IIM; ω2)-, and low (type IIL; ω5)- 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 (ω1) binding site density in the hippocampus of aged rats was also demonstrated in saturation experiments with 3H]zolpidem. This aging-induced increase in 3H]zolpidem binding was also observed in hippocampal membranes from Fischer 344 rats. Moreover, in both rat strains, GABA induced a greater enhancement of 3H]zolpidem (5 nM) binding to type I (ω1) sites (GABA shift) in aged than in adult hippocampal membranes. Quantitative autoradiographic analysis of 3H]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 (ω1) 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. |
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Keywords: | GABAA receptor complex Benzodiazepine (ω) binding isotypes (type I type IIM type IIL) [3H]Zolpidem binding Aging Hippocampus |
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