EFFECTS OF VINCONATE ON AGE-RELATED ALTERATIONS IN [H-3] MK-801, [H-3] GLYCINE, SODIUM-DEPENDENT D-[H-3]ASPARTATE, [H-3] FK-506 AND [H-3] PN200-110 BINDING IN RATS

We investigated the effects of age and yl-3-ethyl-2,3,3a,4-tetrahydro- 1H-indolo[3,2,1-de] [1,5] naphthyridine-6-carboxylate hydrochloride (v inconate), an indolonaphthyridine derivative, on calcium channels, neu rotransmitter receptor systems and immunophilin in Fischer rat brain u sing quantitative receptor autoradiography. [H-3]MK-801, [H-3]glycine, sodium-dependent D-[H-3]aspartate, [H-3]FK-506 and [H-3]PN200-110 wer e used to label N-methyl-D-aspartate (NMDA) receptors, glycine recepto rs, excitatory amino acid transport sites, FK-506 binding proteins (FK BP) and voltage-dependent L-type calcium channels, respectively. [H-3] Glycine and sodium-dependent D-[H-3]aspartate binding significantly de creased in the frontal cortex, parietal cortex, striatum, nucleus accu mbens, hippocampus, thalamus, substantia nigra and cerebellum of 24 mo nth old rats in comparison with 6 month old animals. In contrast, [H-3 ]MK-801, [H-3]FK-506 and [H-3]PN200-110 binding showed no significant change in the brain of 24 month old rats. Intraperitoneal chronic trea tment with vinconate (10 and 30 mg/kg, once a day for 4 weeks) dose-de pendently ameliorated the significant reduction in [H-3]glycine and so dium-dependent D-[H-3]aspartate binding: in the brain of 24 month old rats. These results demonstrate that glycine receptors and excitatory amino acid transport sites are more susceptible to aging processes tha n NMDA receptors, immunophilin and voltage-dependent L-type calcium ch annels. Furthermore, our findings suggest that vinconate may have a be neficial effect on age-related changes in glycine receptors and excita tory amino acid transport sites. (C) 1997 Elsevier Science Ireland Ltd .