title: Investigating the long-term effect of subchronic phencyclidine-treatment on novel object recognition and the association between the gut microbiota and behavior in the animal model of schizophrenia.
abstract: Subchronic phencyclidine (subPCP) treatment induces schizophrenic-like behavior in rodents, including cognitive deficits and increased locomotor sensitivity towards acute administration of PCP. Evidence is accumulating that the gut microbiota (GM) influences behavior through modulation of the microbiota-gut-brain axis, and hence, part of the variation within this animal model may derive from variation in the GM. The aims of this study was to investigate first, the duration of subPCP-induced cognitive impairment in the novel object recognition test, and second, the possible effect of subchronic PCP-treatment on the GM, and the association between the GM and the behavioral parameters. The association was further investigated by antibiotic reduction of the GM. Male Lister Hooded rats were dosed twice daily i.p. with either 5mg/kg PCP or sterile isotonic saline for seven days followed by a seven-day washout period. Rats were tested in the novel object recognition and the locomotor activity assays immediately after, three weeks after, or six weeks after washout, and the fecal GM was analyzed by high throughput sequencing. Antibiotic- and control-treated rats were tested in the same manner following washout. In conclusion, subPCP-treatment impaired novel object recognition up to three weeks after washout, whereas locomotor sensitivity was increased for at least six weeks after washout. Differences in the core gut microbiome immediately after washout suggested subPCP treatment to alter the GM. GM profiles correlated to memory performance. Administration of ampicillin abolished the subPCP-induced memory deficit. It thus seems reasonable to speculate that the GM influences memory performance, contributing to variation within the model.
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1871 Frederiksberg C., Denmark. Electronic address: bmp@sund.ku.dk.
authors.forename: B
authors.initials: B
authors.lastname: Pyndt Jørgensen
authors.affiliation: Department of Food Science, Faculty of Science, University of Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Krych
authors.affiliation: Nonclinical Safety Research, H. Lundbeck A/S, Valby, Denmark.
authors.forename: T B
authors.initials: TB
authors.lastname: Pedersen
authors.affiliation: Synaptic Transmission, H. Lundbeck A/S, Valby, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Plath
authors.affiliation: Synaptic Transmission, H. Lundbeck A/S, Valby, Denmark.
authors.forename: J P
authors.initials: JP
authors.lastname: Redrobe
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1871 Frederiksberg C., Denmark.
authors.forename: A K
authors.initials: AK
authors.lastname: Hansen
authors.affiliation: Department of Food Science, Faculty of Science, University of Copenhagen, Denmark.
authors.forename: D S
authors.initials: DS
authors.lastname: Nielsen
authors.affiliation: Synaptic Transmission, H. Lundbeck A/S, Valby, Denmark.
authors.forename: C S
authors.initials: CS
authors.lastname: Pedersen
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1871 Frederiksberg C., Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Larsen
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1871 Frederiksberg C., Denmark.
authors.forename: D B
authors.initials: DB
authors.lastname: Sørensen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology*; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D064307:Microbiota / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects*; D012559:Schizophrenia / Q000139:chemically induced / Q000382:microbiology*
chemical_list: D006213:Hallucinogens; D010622:Phencyclidine
keywords: Ampicillin; Animal model; Gut microbiota; Locomotor Activity Test; Memory; Novel object recognition; PCP behavior; Phencyclidine; Schizophrenia