Comparative behavioral and pharmacological studies with centrally administered kynurenine and kynurenic acid in rats

Abstract

In the present study the effects of kynurenine and its metabolite kynurenic acid were compared in different behavioral and pharmacological tests. Kynurenic acid administered i.c.v. resulted in ataxia and stereotypy in a dose-dependent manner (0.025–1.6 μmol). Administration of 0.8 μmol of kynurenic acid resulted in sleeping and an approximate 25% mortality of the animals. At a dose of 1.6 μmol all of the animals died within 2–5 min from cardiorespiratory failure. One hour after lower doses of kynurenic acid the behavior of the rats appeared normal (neither stereotypy nor ataxia were observed in their familiar environemnt), but their exploratory activity (0.025–0.2 μmol) was significantly lower in a novel environment (open-field box) compared to the control group. Twenty four hours after the injection of kynurenic acid the exploratory activity of the animals did not differ from the control group. Kynurenine administered i.c.v. in equimolar doses did not result in stereotypy, ataxia, sleeping or mortality of the animals although, immediately after high doses short-lasting (1–2 min) immobility was observed. The rearing activity of the high dose kynurenine-treated animals was lower 1 h after injection, but this effect disappeared 24 h after the treatment. Post-trial injection of kynurenic acid (0.2 μmol) slightly, but not significantly, inhibited the learning ability of the rats in an active avoidance paradigm. Kynurenine administered in an equimolar dose had no effect on the speed of learning, but significantly attenuated the intertriai activity of the rats. Kynurenic acid (0.2 μmol, 0.4 μmol) did not significantly inhibit the passive avoidance latency of the animals after post-trial treamtent. These findings suggest that i.c.v. administration of kynurenic acid results in marked acute behavioral changes while equimolar doses of kynurenine had only slight behavior effects. The present experiments and earlier behavioral data suggest that the NMDA receptor complex plays a role in specific cognitive functions.