title: Maternal lipopolysaccharide treatment differentially affects 5-HT(2A) and mGlu2/3 receptor function in the adult male and female rat offspring.
abstract: Maternal infection during pregnancy increases the risk for the offspring to develop schizophrenia. However, it is still not fully understood which biochemical mechanisms are responsible for the emergence of neuropsychiatric symptoms following prenatal immune activation. The serotonin (5-hydroxytryptamine, 5-HT) and glutamate system have prominently been associated with the schizophrenia pathophysiology but also with the mechanism of antipsychotic drug actions. Here, we investigated the behavioral and cellular response to 5-HT2A and metabotropic glutamate (mGlu)2/3 receptor stimulation in male and female offspring born to lipopolysaccharide (LPS)-treated mothers. Additionally, we assessed protein expression levels of prefrontal 5-HT2A and mGlu2 receptors. Prenatally LPS-exposed male and female offspring showed locomotor hyperactivity and increased head-twitch behavior in response to the 5-HT2A receptor agonist DOI. In LPS-exposed male offspring, the mGlu2/3 receptor agonist LY379268 failed to reduce DOI-induced prepulse inhibition deficits. In LPS-males, the behavioral changes were further accompanied by enhanced DOI-induced c-Fos protein expression and an up-regulation of prefrontal 5-HT2A receptors. No changes in either 5-HT2A or mGlu2 receptor protein levels were found in female offspring. Our data support the hypothesis of an involvement of maternal infection during pregnancy contributing, at least partially, to the pathology of schizophrenia. Identifying biochemical alterations that parallel the behavioral deficits may help to improve therapeutic strategies in the treatment of this mental illness. Since most studies in rodents almost exclusively include male subjects, our data further contribute to elucidating possible gender differences in the effects of prenatal infection on 5-HT2A and mGlu2/3 receptor function.
authors.affiliation: Brain Research Institute, Department of Neuropharmacology, University of Bremen, Bremen, Germany. Electronic address: wischhof@uni-bremen.de.
authors.forename: Lena
authors.initials: L
authors.lastname: Wischhof
authors.affiliation: Brain Research Institute, Department of Neuropharmacology, University of Bremen, Bremen, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Irrsack
authors.affiliation: Center for Biomolecular Interactions, Department of Biology and Chemistry, University of Bremen, Bremen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Dietz
authors.affiliation: Brain Research Institute, Department of Neuropharmacology, University of Bremen, Bremen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D008070:Lipopolysaccharides; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000503:physiopathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011297:Prenatal Exposure Delayed Effects; D065808:Prepulse Inhibition / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology; D012727:Sex Characteristics
chemical_list: D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D044402:Receptor, Serotonin, 5-HT2A; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3
keywords: 5-HT(2A); Maternal infection; PPI; Schizophrenia; mGlu2/3