AGE-RELATED DIMINUTION OF DOPAMINE ANTAGONIST STIMULATED VESAMICOL RECEPTOR-BINDING

Previous studies of radiolabeled vesamicol receptor (VR) ligands sugge st that the latter may be used in conjunction with dopamine D2 antagon ists to measure changes in striatal cholinergic function. In this stud y, the effects of aging on vesicular acetylcholine storage/release wer e investigated with the high-affinity VR ligand (+)-meta-[I-125]iodobe nzyltrozamicol [(+)-[I-125]MIBT]. Methods: Male Fischer 344 rats (aged 3 and 24 mo) were injected either with a vehicle or a D2 antagonist [ haloperidol or S-(-)-eticlopride]. At prescribed intervals thereafter, all animals were intravenously injected with 10 mu Ci of (+)-[I-125]M IBT. Three hours after radiotracer injection, the animals were killed and their brains dissected. The concentration of radio-tracer in the s triatum, cortex and cerebellum were then determined. Results: In contr ol animals, comparable levels of (+)-[I-125]MIBT were observed in corr esponding brain regions of young adult and aged Fischer 344 rats. More over, in haloperidol- and S-(-)-eticlopride-treated young adult rats, striatal levels of (+)-[I-125]MIBT were elevated by 35% and 66%, respe ctively, relative to controls. In contrast, haloperidol treatment fail ed to alter the striatal levels of (+)-[I-125]MIBT in aged rats while S-(-)-eticlopride displayed a twofold reduction in potency in aged rat s. Conclusion: Aging is associated with a reduction in striatal cholin ergic plasticity or striatal cholinergic reserve and that the D2-stimu lated increase in VR ligand binding is a functionally relevant paramet er.