Effects of MK-801, ketamine and alaptide on quinolinate models in the maturing hippocampus

The ability of the N-methyl-D-aspartate receptor antagonists, MK-801, ketamine and alaptide [a newly synthesized cyclo(1-amino-1-cyclopentane-carbonyl-L-alanyl) with protective properties in models of hypoxia], to prevent neuronal degeneration caused by intracerebroventricular application of quinolinic acid was investigated. Neurodegenerative effects of quinolinate in the hippocampal formation were found to increase with the degree of maturity of glutamatergic target structures. A protective potency of the N-methyl-D-aspartate receptor antagonists was observed at all developmental stages studied (12- and 30-day-old and adult rats). MK-801 showed the highest efficacy, alaptide the lowest. These findings suggest a parallelism in maturity of glutamatergic transmission processes as one prerequisite of quinolinate vulnerability and postnatal increases of target fields of the protectives. Application of MK-801 or ketamine after quinolinate injection intensified their protective effects when compared to simultaneous or preadministration. This observation is interpreted as indicating that quinolinate is a prompter of a delayed neurodegenerative process rather than acting immediately as a toxicant.