Research report Prenatal protein deprivation in rats induces changes in prepulse inhibition and NMDA receptor binding Abraham A. Palmer a, * ,1 , David J. Printz b,1 , Pamela D. Butler c , Stephanie C. Dulawa d , Morton P. Printz a a Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA b Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA c Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatry Research, Orangeburg, NY 10962, USA d Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA Accepted 12 September 2003 Abstract Epidemiological studies suggest that prenatal malnutrition increases the risk of developing schizophrenia. Animal models indicate that prenatal protein deprivation (PPD) affects many aspects of adult brain function. We tested the hypothesis that PPD in rats would alter prepulse inhibition (PPI), which is an operational measure of sensorimotor gating that is deficient in schizophrenia patients. Additionally, we examined dopaminergic and glutaminergic receptor binding in the striatum and hippocampus, which have been suggested to play a role in the etiology of schizophrenia. Rat dams were fed normal (25%) or low (6%) protein diets beginning 5 weeks prior to, and throughout pregnancy. The pups were tested at postnatal days (PND) 35 and 56 for PPI. Striatal and hippocampal NMDA receptor, and striatal dopamine receptor binding were quantified post-mortem in a subset of these rats. Female rats exposed to PPD had reduced levels of PPI at PND 56, but not PND 35, suggesting the emergence of a sensorimotor gating deficit in early adulthood. Striatal NMDA receptor binding was increased in PPD females. A decrease in initial startle response (SR) was also observed in all PPD rats relative to control rats. These results suggest that PPD causes age- and sex-dependent decreases in PPI and increases in NMDA receptor binding. This animal model may be useful for the investigation of neurodevelopmental changes that are associated with schizophrenia in humans. D 2003 Elsevier B.V. All rights reserved. Theme: Disorders of the nervous system Topic: Neuropsychiatric disorders Keywords: Prenatal protein deprivation; Prepulse inhibition; Schizophrenia 1. Introduction Schizophrenia is hypothesized to be a neurodevelopment disorder which may stem in part from primary events occurring in utero that give rise to later life manifestations of brain dysfunction [15,17,25,44,48,57,70,72,78,88 – 91]. As early as 1956, prenatal nutritional deficiency was pro- posed as one potential risk factor for the development of schizophrenia [67]. More recently, epidemiological studies of the ‘‘Dutch Hunger Winter’’ have revealed that fetuses exposed to peak famine conditions during the first trimester in utero had an increased risk of developing schizophrenia as adults [43,77,76]. Other epidemiological studies have identified additional prenatal or perinatal factors associated with an increased risk of schizophrenia, including second trimester viral infection [6,58,62] and obstetric complica- tions [22]. Additionally, post-mortem examination of the brains of schizophrenic patients has shown evidence of abnormal neuronal migration [2,4,72], bolstering the thesis that prenatal events may contribute to the neuropathogenesis of schizophrenia. 0006-8993/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2003.09.077 * Corresponding author. Current address: Columbia Genome Center, College of Physicians and Surgeons, Columbia University, Unit 109, Russ Berrie Medical Science Pavilion, Room 513, 1150 St. Nicholas Avenue, New York, NY 10032, USA. Tel.: +1-917-553-8608 (mobile); fax: +1-212- 851-5176. E-mail address: aap2010@columbia.edu (A.A. Palmer). 1 These two authors contributed equally to this work. www.elsevier.com/locate/brainres Brain Research 996 (2004) 193 – 201