Effects of prenatal treatment with methylazoxymethanol acetate on growth, development, reproductive performance, learning ability and behavior in the rat offspring.

Abstract

Jcl:SD rats were treated intraperitoneally with methylazoxy-methanol acetate (MAM acetate) at 0, 5 and 20 mg/kg dosage levels on day 14 of gestation, and were allowed to deliver spontaneously. Their offspring were examined for learning ability in a water T-maze at 10 weeks of age. Examinations of postnatal growth, development, reproductive performance, morphological alterations of the brain and other aspects of behavior were also carried out. The offspring of mothers that received 20 mg/kg of MAM acetate showed a slight decrease (less than 10%) of body weights from birth through adulthood, and slight decreases (2-22%) of liver, kidney, spleen and testis weights at 3 weeks of age as compared to the controls. They also showed slight delays in ear pinna separation, lower incisor eruption, eye and vaginal opening, but had normal appearances and reproductive performance. On the other hand, the cerebrum weights of the offspring in the 20 mg/kg group were approximately 50% less than controls. Microscopically, the micrencephalic offspring showed greatly reduced cerebral hemispheres and abnormal cortical cytoarchitecture. No significant differences were noted between the offspring of the 5 mg/kg of MAM acetate group and the control offspring. In an open-field behavioral tests, the offspring in the 20mg/kg group showed a decrease in the latent period and increases in the number of sections crossed and rearings. Their spontaneous night activity measured by a wheel cage increased as compared with controls. In the triple T-maze, the micrencephalic offspring made 1.4-2.8 times as many errors as controls did throughout trial days. There were no statistically significant differences in the behavioral parameters between the offspring in the 5mg/kg group and the control offspring. However, 2 animals in the 5 mg/kg group did not solve the maze problem within 10 minutes of the observation period while all controls successfully escaped from the maze.