Amino Acids (2008) 35: 157–160 DOI 10.1007/s00726-007-0603-3 Printed in The Netherlands Altered pre-pulse inhibition in adult rats treated neonatally with domoic acid A. L. Adams 1 , T. A. Doucette 1 , and C. L. Ryan 2 1 Department of Biology, University of Prince Edward Island, Charlottetown, PEI, Canada 2 Department of Psychology, University of Prince Edward Island, Charlottetown, PEI, Canada Received June 20, 2007 Accepted August 30, 2007 Published online November 2, 2007; # Springer-Verlag 2007 Summary. Altered functioning of the glutamate system during critical periods of development is believed to play a role in various neurodevelop- mental disorders, such as schizophrenia. Prepulse inhibition (PPI) of the acoustic startle response is deficient in people with schizophrenia. This study investigated the theory that neonatal treatment with domoic acid (DOM), a glutamate agonist, leads to deficient PPI. Results indicate that neonatal treatment with DOM leads to lowered PPI in adult males and an increased startle response in adult females. Keywords: Kainate receptors – Glutamate – Brain development – Pre-pulse inhibition – Schizophrenia Introduction Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system (Ozawa et al., 1998). It is suspected that abnormal glutamate functioning during critical periods of development may be a contrib- uting factor in various neurodevelopmental disorders such as schizophrenia. Altered functioning of the glutamate system during these periods can have long-lasting effects on the developing central nervous system (McDonald and Johnston, 1990). Our current and past research has focused on how neonatal treatment with low, sub-convulsant doses of DOM (a kainate receptor agonist) affects behavior in adulthood. Theoretically, this treatment with DOM re- sults in the glutamate system being activated above the level that would be normal for this developmental stage. Results have shown abnormalities in seizure-like behav- ior, altered responses to novelty, changes in cognitive functioning and altered neuroanatomy (i.e. the hip- pocampus) (Doucette et al., 2003, 2004, 2007; Tasker et al., 2005). While the exact etiology of schizophrenia is not yet known, abnormal glutamate receptor functioning has been linked to this neurodevelopmental disorder (Stone et al., 2007). Additionally, altered cognitive functioning, changes in response to novelty, epilepsy comorbidity and hippocampal changes are consistent with both clinical manifestations of schizophrenia and with the changes that result following neonatal rodent exposure to DOM. Taken together, this pattern of anomalies suggests that early overactivation of the glutamate system during a critical period of development is a possible animal model of schizophrenia. Animal models provide one of the best ways to study the underlying neurobiological mechanisms that contrib- ute to a human disorder such as schizophrenia. Current animal models of schizophrenia are helpful, but far from perfect. To gain a better understanding of this disorder, it is essential to improve upon current models, as well as to pursue evidence of new models which may lead to further breakthroughs. An ongoing issue in the development of animal models of neuropsychiatric disorders such as schizophrenia, is the difficulty in finding common symptoms which are dis- played in various species. For this reason, relatively sim- ple behaviors such as reflexes, often provide invaluable information regarding the suitability of certain animal models. Prepulse inhibition of the acoustic startle response is one such behavioral measure. Observed in many differ- ent species, including rats and humans, PPI is the normal suppression of the startle reflex that occurs when the star- tling stimulus is preceded by a less intense, non-startling stimulus (Graham, 1975). Believed to be controlled by