The glutamatergic system and lead toxicity

grantor: University of TorontoAlthough the molecular mechanisms by which lead (Pb) produces deleterious effects on cognitive function is not well established, alterations in the function of glutamatergic receptors in the developing brain have been implicated. This research examined the effect of glutamatergic agonists and antagonists in rats exposed to chronic postnatal Pb exposure on three behavioral tasks, seizure activity, the Morris water maze (MWM) and the social transmission of food preference (STFP). At the specific dose and duration of Pb exposure employed, the NMDA, but not the AMPA receptor system appears to be involved in seizure activity. In addition, MK-801 (0.1 mg/kg) appeared to be an effective therapeutic dose to reduce seizures. No main effect of Pb was observed in the MWM or the STFP tasks. This research would suggest that Pb may be interacting at the MK-801 site of the NMDA receptor.M.A