Behavioral deficits in rats with minimal cortical hypoplasia induced by methylazoxymethanol acetate.
Methylazoxymethanol, a short-acting antimitotic agent, produces marked cortical hypoplasia in fetuses when injected into pregnant rats. These offspring also have increased cortical concentrations of biogenic amines associated with hyperactivity and learning deficits. In this experiment, rats with a relatively mild degree of methylazoxymethanol-induced cortical hypoplasia were studied to determine whether these neurochemical and behavioral abnormalities persisted. Sprague-Dawley pregnant rats were injected intraperitoneally on day 15 of gestation with methylazoxymethanol acetate (25 mg/kg). Total brain weight was reduced by 12% and cortical slab weight by 28% in methylazoxymethanol-exposed offspring. They were more active than control rats and showed a trend toward slower learning in a swim maze. Affected offspring had increased cortical concentrations of norepinephrine, 5-hydroxyindoleacetic acid, and glycine. There was no significant difference in the concentrations of serotonin gamma-aminobutyric acid, aspartic acid, glutamic acid, or glutamine. Methylazoxymethanol-lesioned animals with mild cortical hypoplasia remained measurably hyperactive and may serve as a model for the study of neurotransmitter and neuropathologic abnormalities associated with hyperactivity in children with microcephaly.
Mercugliano
M
M
Division of Child Development and Rehabilitation, Children's Hospital of Philadelphia, PA 19104.
Hyman
S L
SL
Batshaw
M L
ML
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology*; D001391:Azo Compounds / Q000009:adverse effects*; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007859:Learning Disabilities / Q000209:etiology*; D008746:Methylazoxymethanol Acetate / Q000009:adverse effects*; D008831:Microcephaly / Q000139:chemically induced / Q000150:complications*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains
D001391:Azo Compounds; D008746:Methylazoxymethanol Acetate