Methylazoxymethanol as a developmental model of neurotoxicity.
Behavioral consequences of exposure to toxic chemicals during development often depend on critical periods of exposure. The present study employed the antimitotic agent methylazoxymethanol (MAM) to interfere with neuron proliferation during specific periods of brain development. Behavioral profiles of neonatal rats were obtained after MAM administration on gestational days 15, 19 (G15 or G19) or postnatal day 1 (PN 1). MAM administration on G15 produced neonates with decreased electroconvulsive shock thresholds (TT50) on postnatal day 8 and increased locomotor activity levels from postnatal day 18 through 29. Treatment on G19 resulted in an increased TT50 and a delay in the developmental locomotor activity curve. Pups treated on PN1 displayed decreased levels of activity on postnatal days 12 through 16 and impaired performance on a rotorod at 29 days of age. MAM treatment on G15 produced decreases in forebrain and cortical mass to 51 and 40% of respective control values. MAM administration on PN1 resulted in small but significant decreases in forebrain, cortex and hindbrain and a 35% decrease in cerebellar size. No changes in regional brain weights were measurable in the G19 treatment group. The results indicate that neonatal behavior can be altered in a relatively specific manner by perturbation of neuronal development at critical time periods and that the functional tests employed clearly distinguish among treatment groups. The findings of this study are interpreted in light of previously described neurochemical and morphological effects of antimitotic treatment.
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D001835:Body Weight; D001927:Brain Diseases / Q000139:chemically induced*; D004195:Disease Models, Animal; D004597:Electroshock; D005260:Female; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000209:etiology
D001391:Azo Compounds; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol