Effect 1 of NMDA Receptor Agonist and Antagonist on Nicotine withdrawal induced Hyperexcitability in Mice

Abstract

Kynurenic acid is a recognized broad-spectrum antagonist of excitatory amino acid receptors with a particularly high affinity for the glycine co-agonist site of the N-methyl-D-aspartate (NMDA) receptor complex. D- Cycloserine is a NMDA receptor partial agonist which facilitate in an initiation of nicotine withdrawal symptoms and dependence. Thus, the influence of kynurenic acid treatment on the development and expression of nicotine dependence was tested by using the nicotine withdrawal-induced hyperexcitability paradigm. Mice were provided with a nutritionally balanced control liquid diet as the sole nutrient source on day 0; from day 1–4 (nicotine 25µg), from day 5–7 (nicotine, 50ug) and from day 8–10 (nicotine, 100ug) was incorporated into the liquid diet. On day 11, the nicotine liquid diet was replaced with nutritionally balanced control liquid diet, and nicotine withdrawal-induced hyperexcitability signs were recorded. The results revealed that acute administration of kunurenic acid (50 and 100mg/kg, i.p.) dose-dependently attenuated nicotine withdrawal-induced hyperexcitability signs, and these results were comparable to D- Cycloserine (50 and 100mg/kg, i.p.) Further, chronic administration of kunurenic acid (50 and 100mg/kg, i.p.) to the nicotine diet fed mice markedly attenuated the nicotine withdrawal-induced hyperexcitability signs. In conclusion, the results and evidence suggest that kinurenic acid exhibited an inhibitory influence against nicotine withdrawal-induced hyperexcitability signs, which could be mediated through its neuromodulatory action.