NAP (davunetide) enhances cognitive behavior in the STOP heterozygous mouse-A microtubule-deficient model of schizophrenia

NAP (generic name, davunetide) is an active fragment of activity-dependent neuroprotective protein (ADNP). ADNP -/- embryos exhibit CNS dysgenesis and die in utero. ADNP+/ mice survive but demonstrate cognitive dysfunction coupled with microtubule pathology. NAP treatment ameliorates, in part, ADNP-associated dysfunctions. The microtubule, stable tubule-only polypeptide (STOP) knockout mice were shown to provide a reliable model for schizophrenia. Here, STOP -/- as well as STOP+/ showed schizophrenia-like symptoms (hyperactivity) that were ameliorated by chronic treatment with the antipsychotic drug, clozapine. Daily intranasal NAP treatment significantly decreased hyperactivity in the STOP+/- mice and protected visual memory. (C) 2010 Elsevier Inc. All rights reserved.