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Related Experiment Videos

MK-801 subsensitivity following postweaning lead exposure

D A Cory-Slechta1

  • 1Department of Environmental Medicine, University of Rochester School of Medicine & Dentistry, New York 14642, USA.

Neurotoxicology
|January 1, 1995
PubMed
Summary

Chronic lead exposure in rats reduced sensitivity to MK-801, a non-competitive NMDA receptor antagonist. This suggests lead

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Area of Science:

  • Neuroscience
  • Toxicology
  • Pharmacology

Background:

  • Lead exposure is a significant public health concern.
  • Lead is known to affect neurotransmitter systems, including the glutamatergic system.
  • The NMDA receptor complex is crucial for synaptic plasticity and learning.

Purpose of the Study:

  • To investigate if lead exposure alters behavioral sensitivity to MK-801, a non-competitive NMDA receptor antagonist.
  • To determine the biological relevance of lead's effect on MK-801 binding in vivo.
  • To explore potential glutamatergic system involvement in lead's behavioral toxicity.

Main Methods:

  • Rats were chronically exposed to lead acetate in drinking water from weaning.
  • A drug discrimination paradigm was used to train rats to distinguish MK-801 from saline.
  • Dose-effect curves for MK-801, PCP, CPP, and NMDA were determined in lead-exposed and control rats.

Main Results:

  • Lead exposure resulted in subsensitivity to MK-801, evidenced by shifts in the dose-effect curve.
  • No significant changes in sensitivity to phencyclidine (PCP), CPP, or NMDA were observed.
  • MK-801 and PCP produced dose-related increases in lever responding, while CPP and NMDA did not.

Conclusions:

  • Lead exposure induces subsensitivity to MK-801 in rats.
  • These findings support the hypothesis that lead-induced behavioral toxicity may involve alterations in the glutamatergic system.
  • The study highlights the specific impact of lead on NMDA receptor antagonist sensitivity.

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