Prenatal protein deprivation in rats induces changes in prepulse inhibition and NMDA receptor binding.
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.
Palmer
Abraham A
AA
Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA. aap2010@columbia.edu
Printz
David J
DJ
Butler
Pamela D
PD
Dulawa
Stephanie C
SC
Printz
Morton P
MP
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005333:Fetus; D005973:Glutamine / Q000378:metabolism; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D011488:Protein Deficiency / Q000503:physiopathology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013216:Reflex, Startle / Q000502:physiology*; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology; D012737:Sex Factors; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D004298:Dopamine