Bromodeoxyuridine and methylazoxymethanol exposure during brain development affects behavior in rats: consideration for a role of nerve growth factorand brain derived neurotrophic factor

Rats prenatally exposed to the neurotoxins methylazoxymethanol (MAM) or 5-B romo-2'-deoxyuridine (BrdU) are used as animal models of brain maldevelopme nt. We administered in rats MAM (20 mg/kg), or BrdU (100 mg/kg) or both at gestational day 11. Locomotion was not affected by any prenatal treatment w hereas learning was delayed in the Morris maze in MAM animals. BrdU induced decreased NGF and BDNF levels in the hippocampus. In the parietal cortex p renatal BrdU administration induced NGF potentation associated with decreas ed BDNF. Animals treated with both MAM and BrdU showed also an increased im munopositivity for choline acetyltransferase (ChAT) and low affinity neurot rophins' receptor (p75) in the septum and Meynert's nuclei. These findings suggest that embryonic exposure to MAM and/or BrdU may be useful for studyi ng mechanisms associated with neurodegenerative diseases affecting brain mo rphology and behavior. (C) 2001 Elsevier Science Ireland Ltd. All rights re served.