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Relationships between Pb-induced changes in neurotransmitter system function and behavioral toxicity

D A Cory-Slechta1

  • 1Department of Neurobiology and Anatomy, University of Rochester School of Medicine, NY 14642, USA.

Neurotoxicology
|January 1, 1997
PubMed
Summary

Lead (Pb) exposure disrupts learning and behavior in rats by affecting dopamine and glutamate systems. These neurochemical changes, particularly in the nucleus accumbens, are linked to impaired cognitive function and behavioral deficits.

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Area of Science:

  • Neuroscience
  • Toxicology
  • Behavioral Science

Background:

  • Lead (Pb) exposure is known to impair cognitive functions, including learning and behavior.
  • Previous research suggests a significant role for dopamine systems, particularly in the nucleus accumbens, in mediating these behavioral changes.

Purpose of the Study:

  • To investigate the specific neurochemical systems (dopaminergic and glutamatergic) affected by lead exposure.
  • To elucidate the role of these systems in lead-induced alterations in learning and fixed interval (FI) schedule-controlled behavior.

Main Methods:

  • Administered dopaminergic (DA) and glutamatergic (GLU) compounds to control and Pb-treated rats.
  • Assessed changes in FI schedule-controlled behavior and learning accuracy.
  • Examined D2 and dopamine uptake sites in the nucleus accumbens and striatum.

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  • Used the DA antagonist EEDQ to probe the role of dopamine in the nucleus accumbens.

    • Main Results:

    • Dopaminergic compounds differentially affected FI response rates in control versus Pb-treated rats.
    • Lead exposure caused significant changes in nucleus accumbens D2 and dopamine uptake sites, but not in the striatum.
    • Glutamatergic compounds, but not DA compounds, differentially affected learning accuracy.
    • Learning accuracy correlated positively with glutamate binding sites in controls, but this correlation reversed with Pb exposure.

    Conclusions:

    • Dopamine systems, especially in the nucleus accumbens, are implicated in lead-induced changes in FI behavior.
    • Glutamatergic system disturbances play a crucial role in lead-induced learning impairments.
    • Further research is needed to confirm these findings and explore regional specificity, developmental effects, and reversibility.