DIFFERENTIAL-EFFECTS OF N-METHYL-D-ASPARTATE ON CA2-RAT STRIATUM - IN-VIVO MICRODIALYSIS APPROACH( HOMEOSTASIS IN DEVELOPING AND ADULT)

This in vivo study concerns developmental differences in the sensitivi ty of striatal neurons to N-methyl-D-aspartate (NMDA). Changes in calc ium homeostasis in adult vs immature rats at postnatal days 8-10, evok ed by NMDA, were evaluated by measurements of Ca-45 efflux and of Ca2 taurine and phosphoethanolamine concentrations in striatal microdialy sates. The efflux of [C-14]sucrose was employed in order to measure ch anges in extracellular space volume. In adult rats the addition of 5 m M NMDA for 20 min to the perfusion medium resulted in a 30-40% increas e in Ca-45 efflux, and in a 15% increase in [C-14]sucrose efflux. Ten minutes after NMDA perfusion, Ca-45 and [C-14]sucrose efflux returned to the baseline. No significant changes in Ca2+ or amino acid concentr ations were observed in the dialysate of the adult rat striatum. NMDA perfusion in the striatum of immature rats initially induced a transie nt (5 min) increase in the efflux of Ca-45 (by 13%) and [C-14]sucrose (by 9%). This was followed by a prolonged (lasting 45-50 min) 45% decr ease in Ca-45 efflux, an 80% reduction of Ca2+ concentration, and incr eases in taurine and phosphoethanolamine concentrations in the dialysa te, whereas [C-14]sucrose efflux recovered within 10 min. These data i llustrate differences in the NMDA response between developing and adul t rat striatum. Only in developing rats did NMDA induce a large and pr olonged influx of extracellular calcium to neurons that may explain th e enhanced NMDA neurotoxicity in immature rats;