Age-related decrease of the NMDA receptor-mediated noradrenaline release in rat hippocampus and partial restoration by D-cycloserine.

The release of [3H]noradrenaline ([3H]NA) evoked by N-methyl-D-aspartate (NMDA) from superfused rat hippocampus synaptosomes was monitored during aging. The maximal effects of NMDA decreased with age from 50% (1.5 months) to 10% enhancement (24 months). Quisqualic acid (100 microM) also enhanced [3H]NA release. Its effect decreased with age with a pattern partly different from that of NMDA. Glycine (1 microM) potentiated the [3H]NA releasing effect of 100 microM NMDA. Unexpectedly, the potentiation which amounted to 50% at 1.5 months, reached almost 200% and 300% in the 18- and 24-month-old rats, respectively, thus compensating in part for the age-related loss of the NMDA-induced effect. Concentration-response relationships for glycine at 3 vs. 24 months suggest that the glycine receptor is superresponsive in the aged brain. This may be due to more efficient glycine removal or/and to impaired release since uptake of the amino acid was increased by 350% in 24- vs. 3-month-old rats, while the K(+)-evoked tritium release from synaptosomes prelabeled with [3H]glycine was decreased. D-Cycloserine, although about 10 times less potent than glycine, strongly enhanced the NMDA-evoked [3H]NA release and may prove useful in cognitive deficits associated with aging and dementia.