POSTNATAL METHYLAZOXYMETHANOL - SENSITIVE PERIODS AND REGIONAL SELECTIVITY OF EFFECTS

Work on neonatal MAM exposure has focused primarily on exposure within the first week postpartum, and on resulting hypoplasia]asia or stunti ng of the cerebellum. Rats in this study were exposed to MAM on 4 cons ecutive postnatal days (PND), beginning at one of six ages, from birth through weaning (PND 1, 5, 9, 13, 17, or 21). MAM was administered su bcutaneously in doses of 3, 4, or 5 mg/kg twice per day. Rats were sac rificed at PNDs 28 or 84. The most sensitive age for MAM-induced stunt ing was determined to be PNDs 1-4. When 5 mg/kg MAM was administered t wice daily on PNDs 1-4, body weight was reduced by 24% at age 28 days. Additionally, when compared to control rats, brains of the 28-day-old rats were stunted as follows: whole brain (11%), cerebellum (35%), hi ppocampus (11%), and olfactory bulb (27%). The effects of PND 1-4 MAM exposure were still evident at 84 days of age when cerebellum and olfa ctory bulbs from treated rats weighed 30% less than those same regions in control rats. These findings indicate that neonatal exposure to MA M results in permanent stunting in select regions of developing rat br ain. This stunting, along with other known MAM effects, can be tailore d by exposure age and dose to augment the use of MAM as a positive con trol for investigation of compounds with neurotoxic potential.