1. Sponsor Organization: NIH/NIEHS

2. Project Title: 05903-04 NMDA RECEPTOR AND BEHAVIORAL TOXICITY OF LEAD

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus: Exposure Assessment

4. Description:

Recently published cellular and biochemical studies suggest that Pb exposure may impair learning and memory functions through an inhibitory action on the NMDA receptor complex. For such a contention to have credence or clinical significance, however, requires that NMDA-based sensitivity can be altered at a behavioral level and/or that compounds acting at the NMDA receptor complex could alter Pb-induced changes in learning. New data from this laboratory supporting that contention include an attenuation and potentiation, respectively, of the accuracy-impairing effects of the non-competitive NMDA antagonist MK-801 and the glutamate agonist NMDA in Pb-exposed rats relative to controls on a multiple schedule of repeated learning (repeated acquisition) and performance. The proposed experiments seek, first, to determine using drug discrimination and receptor autoradiography procedures, the nature of Pb-induced changes in NMDA and MK-801 sensitivity at the level of the whole animal, any correspondence between sensitivity changes and NMDA receptor complex changes, and the conditions under which sensitivity changes occur, including the role of developmental period of exposure (including postnatal, postweaning and adult), associated blood and brain Pb levels, and the importance of a prior behavioral history of drug discrimination. Using a multiple schedule of repeated acquisition (learning) and performance combined with receptor autoradiography, the proposal also seeks to further explore the role of Pb-induced changes in the NMDA receptor complex to Pb-induced learning impairments, by determining whether other noncompetitive antagonist effects on this baseline are also

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Rats
• Study Type:
  • In Vivo
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Neurological
• Hormonal Measures:
• Level Of Study:
• Chemistry Metabolism:
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Lead

11. Performing Institution:

• UNIVERSITY OF ROCHESTER

12. Contact:

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