title: Prenatal lipopolysaccharide treatment enhances MK-801-induced psychotomimetic effects in rats.
abstract: The aim of this study was to evaluate the effect of prenatal lipopolysaccharide (LPS) treatment, which is an animal developmental model of schizophrenia, on MK-801-induced psychotomimetic behavioral changes and brain aminergic system activity in adult offspring. Repeated LPS (1 mg/kg) injection in rats, that had started from 7th day of pregnancy and was continued every second day till delivery, resulted in a long-lasting disruption of prepulse inhibition (PPI) and elevation of locomotor activity in their offspring. The prenatally LPS-treated rats showed hypersensitivity to MK-801 (0.1 and 0.4 mg/kg) as evidenced by the enhancement of acoustic startle amplitude, reduced PPI, and enhanced locomotor activity. These behavioral changes were accompanied by a decrease in the dopamine and its metabolite, DOPAC concentration in the frontal cortex, enhanced dopaminergic system activity in the striatum and no changes in noradrenaline (NA) level. Furthermore, the significant augmentation of 5-HT and 5-HIAA content in the frontal cortex of females only was detected. No changes in the cortical NA tissue level were found. Summing up, the present study demonstrated that the activation of the immune system in prenatal period led to persistent behavioral hypersensitivity to psychotomimetic action of a non-competitive NMDA receptor antagonist, and attention/information processing deficits. The foregoing data indicate that prenatal administration of LPS model some of the clinical aspects of schizophrenia and these behavioral effects are connected with neurochemical changes.
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. basta@if-pan.krakow.pl
authors.forename: A
authors.initials: A
authors.lastname: Basta-Kaim
authors.forename: K
authors.initials: K
authors.lastname: Fijał
authors.forename: B
authors.initials: B
authors.lastname: Budziszewska
authors.forename: M
authors.initials: M
authors.lastname: Regulska
authors.forename: M
authors.initials: M
authors.lastname: Leśkiewicz
authors.forename: M
authors.initials: M
authors.lastname: Kubera
authors.forename: K
authors.initials: K
authors.lastname: Gołembiowska
authors.forename: W
authors.initials: W
authors.lastname: Lasoń
authors.forename: K
authors.initials: K
authors.lastname: Wędzony
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D008070:Lipopolysaccharides; D012701:Serotonin; D016291:Dizocilpine Maleate; D004298:Dopamine; D009638:Norepinephrine