FUNCTIONAL-EFFECTS OF METHYLAZOXYMETHANOL-INDUCED CEREBELLAR HYPOPLASIA IN RATS

The behavioral effects of a series of methylazoxymethanol acetate (MAM ) injections in neonatal rats were investigated. Pups were injected tw ice daily on days 5-8 after birth with 4 mg/kg MAM or saline. Similar treatment paradigms cause cerebellar hypoplasia, which is a result of a depletion of granule cells. MAM treatment reduced adult cerebellar w eight to 92% that of control and was without effect on weight of other brain regions examined. Postweaning body weight gain in males was red uced. Nest odor preference and emergence (light/dark box) assessments indicated no significant effects. Complex maze assessments and perform ance in an operant test battery demonstrated no cognitive deficits. In deed, MAM-treated females performed better in a complex maze under lig hted conditions than same-sex controls. Open field and running wheel a ctivity levels in females were unaffected. Though not statistically si gnificant, males exhibited a mild hyperactivity syndrome characterized by an increase in running wheel and open field activity, as well as a depressed startle response. Both sexes were hypersensitive to the loc omotor-increasing effects of methamphetamine. These results suggest th at the functional effects resulting from cerebellar hypoplasia produce d by MAM treatment on PNDs 5-8 are milder than those resulting from MA M treatment beginning on the day of birth, The results are compared wi th other forms of cerebellar lesions and provide support for the hypot hesis that early insult (day of birth or shortly after) produces hypoa ctivity whereas a later insult (day 4 or later after birth) produces a syndrome of hyperactivity.