Neonatal domoic acid treatment produces alterations to prepulse inhibition and latent inhibition in adult rats

Schizophrenia is a complex and severe mental disorder characterized by positive, negative and cognitive symptoms. Characteristic behavioral alterations reflecting these categories of symptoms have been observed in many animal models of this disorder, and are consistent with those manifested in the clinical population. The purpose of this study was to determine whether early alterations in glutamate signaling would result in alterations to prepulse inhibition (PPI) and latent inhibition (LI); two assessments used for evaluating putative novel animal models with relevance to schizophrenia. In the present experiment, daily subcutaneous (s.c.) injections of 20 μg/kg of domoic acid (DOM) were administered to rat pups from postnatal days (PND) 8-14. When tested as adults, DOM treated rats displayed deficits in PPI that were dependant on both sex and time of day. No differences in startle amplitude, habituation, or movement were found during any test, indicating that the PPI deficits seen could not be attributed to baseline startle differences. Deficits in LI were also apparent when adult rats were tested using a conditioned taste aversion task, with DOM-treated animals displaying a significantly suppressed LI. These results suggest that early treatment with DOM may serve as a useful tool to model schizophrenia which in turn may lead to a better understanding of the contribution of glutamate, and in particular, kainate receptors, to the development and/or manifestation of schizophrenia or schizophrenia-like symptoms in the clinical population.