Behavioral effects of methylazoxymethanol-induced micrencephaly.
This study was prompted by reports of functionally normal humans with micrencephaly or cortical hypoplasia. Methylazoxymethanol acetate (MAM) treatment, which induces micrencephaly in rats, was administered by injection (20 mg/kg) on gestational day 14. Prior to weaning and into adulthood, offspring were assessed on many behavioral tests. There were 3 findings. First, MAM rats (forebrain weight less than 2/3 of controls) were not profoundly hyperactive. Increased activity was seen only on prolonged tests or after amphetamine administration. Second, MAM rats were hypoactive in some conditions. These rats were light shy and less likely to explore lighted areas. MAM rats appeared hyperreactive to environmental stimuli, but not hyperactive. Finally, no MAM effect on behavior was as large as that on brain weight. Thus, as with clinical findings, rat micrencephalics are more remarkable for functional sparing than for behavioral abnormalities.
Ferguson
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SA
Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
Racey
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Paule
M G
MG
Holson
R R
RR
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D009949:Orientation / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011340:Problem Solving / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000477:Alkylating Agents; D008694:Methamphetamine; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol