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Injection of the endogenous tryptophan metabolite, quinolinic acid (120 nmol in 1.0 microliter) unilaterally into the basal forebrain of rats resulted in a significant ipsilateral decrease in cortical choline acetyltransferase activity, suggesting that cholinergic cells of the nucleus basalis magnocellularis (nbm) were damaged. Injected animals also showed a significant deficit in performance on an 8-arm radial maze, compared to sham operated controls, indicating an impairment of memory. Co-injection of another endogenous tryptophan metabolite, kynurenic acid (360 nmol in 1.0 microliter) with quinolinic acid afforded an almost complete protection against the neurotoxic and memory-impairing effects of quinolinic acid alone. These findings support previous reports that kynurenic acid can protect against the neurotoxic effects of quinolinic acid and indicate for the first time that kynurenic acid can also protect against impairments of memory produced by injection of quinolinic acid into the nbm.
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