Kynurenic Acid Regulation of Stimulus Processing

Dartmouth College, Hanover NH

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Abstract

[unreadable] DESCRIPTION (provided by applicant): This proposal tests the hypothesis that elevated levels of brain kynurenic acid (KYNA) interferes with attentional processing. These studies will assess the effect of elevating endogenous KYNA on decreases in attention to an irrelevant cue in a latent inhibition task and the ability to selectively increase and decrease attention to a discrete cue in a blocking/unblocking procedure. It is predicted that elevated KYNA will prevent the normal decrease in attention to a pre-exposed stimulus, thereby reducing the latent inhibition effect and interfere with decreases in attention during blocking while leaving unblocking unaffected. These predictions are based on several lines of evidence. First, KYNA is an endogenous antagonist of the alpha7 nicotinic acetylcholine receptor, a receptor that has been implicated in attentional processing. Secondly, KYNA levels are elevated in disorders characterized by attention impairments, including schizophrenia. Specifically, persons with schizophrenia exhibit reductions in latent inhibition and blocking. In addition, recent evidence suggests that elevated KYNA can disrupt sensory gating processes, like those that are disrupted in schizophrenia, providing a compelling case for a more general role for KYNA in stimulus selection and suppression. [unreadable] [unreadable] [unreadable]