Methylazoxymethanol-induced micrencephaly in the Brown Norway strain: behavior and brain weight

Abstract

A single injection of 20 mg/kg methylazoxymethanol acetate (MAM) on gestational day 14 in Brown Norway rats produced micrencephalic offspring (whole brain ≈65% of control). Despite the micrencephaly, 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 activity, and emergence behavior using a light/dark apparatus were not significantly 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 microencephaly. Behav. Neurosci.107, 1–10], frontal cortex and striatum weights were more reduced in Brown Norway micrencephalics. The MAM-induced behavioral alterations in the Brown Norway strain may have appeared attenuated compared to alterations shown by MAM-treated Sprague–Dawley rats due to differences in baseline behavior between these two strains. Compared to control Sprague–Dawley rats in the previous study, control Brown Norway rats were more active in the open field and running wheels, but less active in the complex maze, exhibiting little to no learning. Emergence tests indicated increased dark preference in Brown Norway rats. Baseline behavior (increased activity and light shyness) of control Brown Norway rats was similar to that of MAM-treated Sprague–Dawley rats; a potential confound in the detection of behavioral effects of a compound. These findings emphasize the effects that strain selection may have on the outcome and interpretation of toxicological/teratological studies.