Pharmacological and neurochemical investigations of lead-induced hyperactivity

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Abstract

Mice chronically exposed to inorganic lead from birth, demonstrate levels of spontaneous motor activity approximately three times higher than coetaneous controls. In addition, their behavioural responses to (+)- and (-)-amphetamine, methylphenidate, and phenobarbital are altered. To further clarify the mechanism of action of lead involved in the induction of hyperactivity and altered pharmacological response, lead-treated mice were administered apomophrine, atropine, neostigmine, physostigmine, α-methylparatyrosine, benztropine, chlorpromazine, l-3,4-dihydroxyphenylalanine (l-Dopa), fenfluramine and 2-dimethylaminoethanol. A comparison of the effects of these compounds on motor activity and reactivity showed significant differences between control and lead-treated hyperactive mice. Neurochemical investigations of lead-induced hyperactivity were undertaken in chronically treated hyperactive mice by measurement of steady state levels and of synaptosomal transport. The so-called high affinity transport systems were studied for the following putative neurotransmitters, precursors, and amino acids: choline, tyrosine, phenylalanine, norepinephrine, dopamine, leucine, glycine, 5-hydroxytryptamine and γ-aminobutyric acid. Significant changes in high affinity synaptosomal transport were found for choline, dopamine and tyrosine. The transport systems of other suspected neurotransmitters and the amino acid leucine were not different between lead-treated and coetaneous control mice. In addition, steady-state levels of acetylcholine, dopamine, and norepinephrine were measured in forebrains. Norepinephrine levels were increased, while dopamine and acetylcholine levels were not different in lead-treated animals.

Original languageEnglish (US)
Pages (from-to)431-444
Number of pages14
JournalNeuropharmacology
Volume14
Issue number5-6
DOIs
StatePublished - Jan 1 1975

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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