METHYLAZOXYMETHANOL-INDUCED MICRENCEPHALY IN THE BROWN-NORWAY STRAIN - BEHAVIOR AND BRAIN-WEIGHT

A single injection of 20 mg/kg methylazoxymethanol acetate (MAM) on ge stational day 14 in Brown Norway rats produced micrencephalic offsprin g (whole brain approximate to 65% of control). Despite the micrencepha ly, MAM-induced alterations in behavior assessed here were relatively mild. The MAM-treated rats exhibited increased activity under darkened conditions in a complex maze and marginally increased activity after a challenge of methamphetamine. Open field activity, running wheel act ivity, and emergence behavior using a light/dark apparatus were not si gnificantly affected. Compared with a similar study of Sprague-Dawley micrencephalics [Ferguson S. A., Racey F. D., Paule M. G. and Holson R . R. (1993) Behavioral effects of methyloxymethanol-induced microencep haly. Behav. Neurosci. 107, 1-10], frontal cortex and striatum weights were more reduced in Brown Norway micrencephalics. The MAM-induced be havioral alterations in the Brown Norway strain may have appeared atte nuated compared to alterations shown by MAM-treated Sprague-Dawley rat s due to differences in baseline behavior between these two strains. C ompared to control Sprague-Dawley rats in the previous study, control Brown Norway rats were more active in the open field and running wheel s, but less active in the complex maze, exhibiting little to no learni ng. Emergence tests indicated increased dark preference in Brown Norwa y rats. Baseline behavior (increased activity and light shyness) of co ntrol Brown Norway rats was similar to that of MAM-treated Sprague-Daw ley rats; a potential confound in the detection of behavioral effects of a compound. These findings emphasize the effects that strain select ion may have on the outcome and interpretation of toxicological/terato logical studies.