THE DEVELOPMENT OF MK-801, KAINATE, AMPA, AND MUSCIMOL BINDING-SITES IN CAT VISUAL-CORTEX

Previous work using homogenate binding has shown that the development of 0,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10imine maleate (MK-801) binding in cat visual cortex increases from 21 days to 42 days, the h eight of the plastic period, and decreases in adulthood. We have studi ed the generality of this finding by examining the development of NMDA binding sites in several brain regions and by examining the developme nt of other binding sites in the visual cortex. After confirming the o riginal finding, we extended it by showing that the sensitivity of MK- 801 binding sites to glutamate and glycine decreases when the cat beco mes an adult. We then examined the regional specificity of MK-801 bind ing. Retinal binding did not change significantly with age. Binding in both visual cortex and hippocampus increased significantly from 7 day s to 42 days regardless of whether binding was measured per milligram wet weight or per milligram protein. The decline from 42 days to adult hood was less dramatic in the hippocampus than in the visual cortex an d was statistically significant only when binding was measured per mil ligram protein. Saturation analyses also showed a difference in the tw o structures. B-max in the visual cortex, but not in the hippocampus, decreased from 42 days to adulthood. To determine whether these develo pmental changes were specific to MK-801 binding sites, we compared the age-dependent binding of MK-801, kainate, alpha-amino-3 -hydroxy-5-me thyl-4-isoxazolepropionic acid (AMPA), and muscimol. Like MK-801, kain ate binding increased from 7 days to 42 days and decreased from 42 day s to adulthood. AMPA and muscimol binding showed a similar increase in binding from 7 days to 42 days but did not decrease significantly fro m 42 days to adulthood. Displacement experiments suggest that AMPA and kainate bind to separate sites. The 42-day peak in NMDA and kainate b inding suggests that their associated receptors may have a role in det ermining the plastic period of visual cortex.