Cognitive deficits caused by late gestational disruption of neurogenesis in rats: a preclinical model of schizophrenia.
Late gestational disruption of neurogenesis in rats has been shown to induce behavioral abnormalities thought to mimic aspects of positive and negative symptoms of schizophrenia. Furthermore, it has been shown that the morphological changes produced by the perturbation are relevant to schizophrenia with reduced thickness of the hippocampus, thalamus, and cortical regions. In addition to the positive and negative symptoms, schizophrenia is associated with deficits in a wide variety of cognitive domains. In the present studies, we assessed whether the cognitive deficits are modeled by disruption of neurogenesis late during gestation (gestational day 17) in the rat. In the battery of tests utilized, we describe that rats in which neurogenesis was disrupted have deficits in a reversal-learning paradigm of the Morris water maze and in object recognition, and that they exhibit perseveration in the Porsolt forced swimming test. Additionally, we found deficient associative learning in an acquisition of an active avoidance paradigm and deficits in latent inhibition. No deficits were observed in the reference memory version of the Morris water maze and in a non-match-to position experiment, showing that the deficits are limited to certain aspects of cognition.
Flagstad
Peter
P
Department of Pharmacology Target Research, H Lundbeck A/S, Copenhagen-Valby, Denmark. PFLA@Lundbeck.com
Glenthøj
Birte Y
BY
Didriksen
Michael
M
D000818:Animals; D001245:Association Learning / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D018782:Maze Learning / Q000187:drug effects; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D009420:Nervous System / Q000187:drug effects / Q000196:embryology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D012193:Reversal Learning / Q000187:drug effects; D012559:Schizophrenia / Q000139:chemically induced*; D013550:Swimming / Q000523:psychology; D013723:Teratogens / Q000633:toxicity
D013723:Teratogens; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol