Raising Endogenous Brain Levels of Kynurenic Acid May Produce Anti-Reward and Enhance Suicide Ideation

Abstract

While we applaud the elegant research in animals by our NIDA colleagues and their arduous attempt to find a novel treatment for Cannabis abuse, unfortunately we disagree with their suggestion to raise brain kynurenic acid. However, we do agree with their premise that raising kynurenic acid will indeed reduce neuronal release of dopamine at mesolimbic sites. There are a number of reports showing that kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. In fact it is known that KYNA levels can be enhanced in the brain by even dietary tryptophan. Essentially, the neuro-inhibitory tryptophan metabolite kynurenic acid (KYNA) is a preferential antagonist of the α7 nicotinic acetylcholine receptor (α7nAChR). Interestingly, it was found that administration of 1.5% tryptophan added diet reduced the extracellular DA level to 60%, and increased the extracellular KYNA to 320% in the striatum of rodents .