POSTWEANING LEAD-EXPOSURE ENHANCES THE STIMULUS PROPERTIES OF N-METHYL-D-ASPARTATE - POSSIBLE DOPAMINERGIC INVOLVEMENT

This study sought to determine whether previously reported Pb-induced biochemical changes in the NMDA receptor complex also resulted in chan ges in NMDA sensitivity in vivo. Rats chronically exposed to 0, 50 or 150 ppm Pb acetate in drinking water postweaning were trained to discr iminate the stimulus properties of 30 mg/ kg NMDA from sa line using s tandard operant food-reinforced drug discrimination procedures. Follow ing acquisition of the discrimination, various doses of NMDA, of the c ompetitive antagonist CPP, the D-2 antagonist spiperone and the D-1 an tagonist SCH23390 were substituted for the NMDA training dose and perc ent NMDA responding to each determined. In addition, the efficacy of C PP in antagonizing the NMDA stimulus was assessed. NMDA increased drug lever responding to levels >90%, an effect antagonized by CPP. Spiper one substituted for NMDA, whereas SCH23390 engendered partial substitu tion and CPP on ly minima I substitution. Pb exposure did enhance NMDA sensitivity, as indicated by an increased frequency of full NMDA subs titution at lower NMDA doses, although the effect size was somewhat mo dest Pb exposure, at least at one dose, also attenuated the substituti on of spiperone for NMDA, raising the possibility that dopaminergic sy stems may be involved in mediating Pb-induced changes in NMDA sensitiv ity. (C) 1996 Intox Press, Inc.