D-cycloserine enhances spatial learning performances of rats chronically exposed to lead during the developmental period.

Abstract

Chronic developmental lead (Pb) exposure has long been associated with cognitive dysfunction in children and animals. N-methyl-D-aspartate (NMDA) receptors, important in the synaptic mechanisms involved in learning and memory, are key target of lead toxicity. D-cycloserine (DCS), a partial agonist of the NMDAassociatedglycine site, has been recognised as a potential cognitive enhancer.We investigated the potential effects of Pb exposure (lead acetate 0.2% through the drinking water) during gestation and lactation (GL), on the spatial learning and memory capacities of PN32 rats. We also evaluatethe ability of DCS (30 mg/ml), administered daily 24h after weaning during 15 days, to attenuate Pb neurotoxicity-induced cognitive deficits. Results indicate that rats exposed to lead during gestation and lactation have a significantly increased latency to find the hidden platform and cover a significant longer distance compared to control-vehicle in the learning phase of the Morris water maze. However, the administration of DCS to GL animals improved significantly their learning performances compared with GL-vehicle. In contrast, there is no significant difference between all groups during the probe test and the visual cue test. In conclusion, DCS enhancement of the NMDA receptor function is an effective strategy to ameliorate neurotoxicity leadassociated spatial learning deficits.