Nanomolar concentrations of kynurenic acid reduce extracellular dopamine levels in the striatum

Precise regulation of dopaminergic activity is of obvious importance for the physiology and pathology of basal ganglia. We report here that nanomolar concentrations of the astrocyte-derived neuroinhibitory metabolite kynurenic acid (KYNA) potently reduce the extracellular levels of striatal dopamine in unanesthetized rats in vivo. This effect, which is initiated by the KYNA-induced blockade of alpha7 nicotinic acetylcholine receptors, highlights the functional relevance of glia-neuron interactions in the striatum and indicates that even modest increases in the brain levels of endogenous KYNA are capable of interfering with dopaminergic neurotransmission.