Alteration of central cholinergic function by chronic lead acetate exposure

Paul T. Carroll, Ellen K. Silbergeld, Alan M. Goldberg

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Mice chronically exposed to lead during initial periods of development demonstrate increased levels of spontaneous motor activity. Their behavioral responses to a number of drugs indicate a decrease in central cholinergic activity. Studies utilizing peripheral nervous tissue have shown a decreased evoked and an elevated spontaneous release of ACh by lead. The possibility was examined, therefore, that the evoked and spontaneous ACh release in brain tissue might be similarly altered by chronic lead treatment in vivo. The results indicate that chronic lead administration inhibits the potassium-induced release of both choline and ACh from cortical minces. Potassium-induced release of labeled ACh synthesized from labeled choline is also significantly impaired in the lead-treated animals. Administration of methylphenidate to lead-treated animals, previously reported to suppress leadinduced hyperactivity, reverses the inhibition of potassium-induced choline and ACh release. Spontaneous release of ACh in lead-treated animals is significantly increased. Omission of calcium significantly inhibits the potassium-induced release of ACh without significantly altering choline release. No changes were found in the steady state levels of choline and ACh nor in the activities of choline acetyltransferease, choline phosphokinase, and acetylcholinesterase in the brains of lead-treated animals during development. The results suggest that the inhibition of potassium-induced release of ACh by lead may occur by two different mechanisms: (1) lead may reduce the availability of choline for ACh synthesis, and (2) lead may interfere with the role of calcium in the evoked release of ACh. The present work indicates that chronic lead exposure, at doses previously shown in mice to elicit hyperactivity, also disrupts central ACh function. Also, the results indicate that lead may be a valuable tool in elucidating the dynamic processes involved in central ACh metabolism.

Original languageEnglish (US)
Pages (from-to)397-402
Number of pages6
JournalBiochemical Pharmacology
Issue number5
StatePublished - Mar 1 1977

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology


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