title: The prenatal methylazoxymethanol acetate treatment: a neurodevelopmental animal model for schizophrenia?
abstract: The prenatal methylazoxymethanol acetate (MAM) treatment has been proposed as a suitable model for the neurodevelopmental aspects of schizophrenia since the morphological abnormalities it induces in the brain are subtle and in line with most reports of neuropathology in schizophrenic brains. However, the functional aspects of this treatment have not been investigated with behavioural paradigms that are relevant for the psychopathology of the symptoms of schizophrenia. In the present study, we investigated the validity of the prenatal MAM treatment as a developmental model for schizophrenia with a prepulse inhibition of the acoustic startle reflex, latent inhibition, locomotor activity, and cognition and emotionality with freezing in fear conditioning paradigms. We have conducted two studies: in Study I, MAM was injected from E09 to E12, and in Study II MAM was administered at later stages in the embryonic development, from E12 to E15. Morphologically, the prenatal MAM treatment induced mild to severe reduction in brain weights and in the entorhinal cortex, prefrontal cortex and striatum volumes, the severity of the effects depending on the timing of administration. However, despite the morphological abnormalities induced by the MAM treatments, no behavioural deficits were observed in the MAM-treated animals when compared to Controls in prepulse inhibition, latent inhibition with the two-way active avoidance, and in the freezing paradigms. Therefore, due to the consistent lack of treatment effect observed in the present investigation, we conclude that the prenatal MAM treatment has no validity as a behavioural model for schizophrenia.
authors.affiliation: Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology, Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Jongen-Rêlo
authors.forename: Andreas
authors.initials: A
authors.lastname: Leng
authors.forename: Marcel
authors.initials: M
authors.lastname: Lüber
authors.forename: Helen H J
authors.initials: HH
authors.lastname: Pothuizen
authors.forename: Liz
authors.initials: L
authors.lastname: Weber
authors.forename: Joram
authors.initials: J
authors.lastname: Feldon
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004622:Embryo, Mammalian / Q000187:drug effects*; D004644:Emotions / Q000187:drug effects; D005260:Female; D007266:Inhibition, Psychological; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000139:chemically induced*; D012565:Schizophrenic Psychology; D012737:Sex Factors
chemical_list: D011500:Protein Synthesis Inhibitors; D008746:Methylazoxymethanol Acetate