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

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 NMDA associated glycine 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 evaluate the 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 lead-associated spatial learning deficits. Keywords: Neurotoxicity; Lead; Development; D-Cycloserine; Learning; Rat. Des etudes faites chez l’homme et l’animal montrent qu’une exposition chronique au plomb durant le developpement provoque des alterations des fonctions cognitives. Les recepteurs au glutamate de type Nmethyl-D-aspartate (NMDA), importants dans les mecanismes synaptiques impliques dans l’apprentissage et la memoire, sont les principales cibles du plomb. Il a ete montre que le D-cycloserine, un agoniste partiel du site glycine associe aux recepteurs NMDA, peut ameliorer les fonctions cognitives. Nous avons etudie les effets possibles d’une exposition au plomb (acetate de plomb 0.2% dans l’eau de boisson) pendant la gestation et la lactation (GL), sur les performances d’apprentissage spatial et de memorisation chez des rats âges de 32 jours. Nous avons egalement evalue la capacite du D-cycloserine (30 mg/ml), administre quotidiennement 24h apres le sevrage durant 15 jours, a attenuer les deficits cognitifs induits par le plomb. Nos resultats indiquent que les rats exposes au plomb pendant la gestation et la lactation mettent signicativement plus de temps et parcourent une plus grande distance que les animaux controle pour trouver la plateforme immergee au cours de la phase d’apprentissage de la piscine de Morris. Toutefois, l’administration de DCS aux animaux GL ameliore significativement leurs performances d’apprentissage comparees a celles des animaux GL non traites au DCS. Aucune difference de motivation ou des capacites de guidage visuo-moteur ne sont presents chez les GL. Donc, l’amelioration de la fonction des recepteurs NMDA pourrait etre une strategie efficace pour ameliorer les deficits d’apprentissage spatial associes a la neurotoxicite au plomb. Mots cles: Neurotoxicite; Plomb; Developpement; D-Cycloserine; Apprentissage; Rat.