Working memory deficits in adult rats after prenatal disruption of neurogenesis.
We investigated the cognitive consequences of a prenatal injection of the mitotic inhibitor methylazoxymethanol (MAM) into pregnant rats at embryonic day 15 (E15) or 17 (E17). The male offspring were tested when adult on a version of the radial-arm maze task that assesses spatial working memory with an extended delay, where performance is dependent, in part, on the hippocampal-prefrontal circuit. A major impairment of spatial learning was observed in E15 MAM rats. However, the E17 MAM rats did learn the rule but were impaired selectively in the 30-min delay-interposed task. Morphologically, the E15 MAM rats exhibited dramatic gross brain abnormalities, whereas the E17 MAM animals displayed aberrant cell migration in the hippocampus and a disrupted laminar pattern in the neocortex. These results suggest that late gestational MAM injection (E17) causes a cognitive impairment in a prefrontal cortex-hippocampus-dependent working memory task. This approach could provide a new developmental model of disorders associated with working memory deficits, such as schizophrenia.
Gourevitch
R
R
INSERM E0117, Hôpital Sainte-Anne, 2 ter rue d'Alésia, Paris, France. gourevitch@chsa.broca.inserm.fr
Rocher
C
C
Le Pen
G
G
Krebs
M-O
MO
Jay
T M
TM
D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006624:Hippocampus / Q000002:abnormalities* / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology*; D008746:Methylazoxymethanol Acetate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D017397:Prefrontal Cortex / Q000002:abnormalities* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol