PEDIATRICS Vol. 85 No. 3 March 1990, pp. 432-436
This Article
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mercugliano, M.
Right arrow Articles by Batshaw, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mercugliano, M.
Right arrow Articles by Batshaw, M. L.

Behavioral Deficits in Rats With Minimal Cortical Hypoplasia Induced by Methylazoxymethanol Acetate

Marianne Mercugliano MD1, Susan L. Hyman MD1, and Mark L. Batshaw MD1

1 From The Children's Seashore House, Division of Child Development and Rehabilitation, Children's Hospital of Philadelphia, Department of Pediatrics, The University of Pennsylvania; and The Kennedy Institute for Handicapped Children and the Department of Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland

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, ggr-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.

Key Words: attention deficit hyperactivity disorder • hyperactivity • methylazoxymethanol • microencephaly • microcephaly • rat