PDE10A inhibition reverses subchronic PCP‐induced deficits in attentional set‐shifting in rats

• DOI: 10.1111/j.1460-9568.2005.03937.x
• Publication Date: 2005-03-09T13:21:03Z
• Authors: Joshua S. Rodefer; Emily R. Murphy; Mark G. Baxter
• Keywords: Phencyclidine

Abstract Persistent suppression of N ‐methyl‐ d ‐aspartate (NMDA) receptor function produces enduring structural changes in neocortical and limbic regions a pattern similar to reported schizophrenia. This similarity suggests that chronic NMDA antagonism animals may represent useful model neurobiological related cognitive deficits Schizophrenia is associated with impairments frontal lobe‐dependent functions, including working memory attentional shifting. Deficits attention executive have not been well characterized animal models schizophrenia using antagonist administration. We investigated whether subchronic systemic administration the phencyclidine (PCP) rats followed by drug washout period would produce on an set‐shifting task. The task functionally analogous sensitive test humans non‐human primates. Subchronic PCP selectively impaired extradimensional shift learning without affecting other discrimination or reversal tasks. Moreover, acute treatment PDE10A inhibitor papaverine immediately prior testing attenuated PCP‐induced across range doses. These data suggest effectively some are observed schizophrenia, inhibition be effective therapeutic route improve