TY - JOUR
T1 - Pharmacological and neurochemical investigations of lead-induced hyperactivity
AU - Silbergeld, Ellen K.
AU - Goldberg, A. M.
N1 - Funding Information:
Acknowledgements-Thaeu thorsw ish to acknowledgeth e following pharmaceuticaclo mpaniesf or supplying compoundsf or this research:S mith, Kline and French, chlorpromazine;R iker, dimethylaminoethanoAl;. H. Robins, fenfluraminea; nd Ciba-Geigy, methylphenidateT.h is researchw as supportedi n part by EHS grants 0034 and 00454.A ResearchS tarter Award from the PharmaceuticaMl anufacturersA ssociation Foundation to E.K.S. also provided support.E .K.S. is a recipiento f a Joseph P. Kennedy, Jr. Fellowship in NeurosciencesT. he authors would like to acknowledget he assistanceo f CANDACE B. PERT in setting up transport studies,a nd of THOMASK EITH TOMOSKYin assaysf or dopaminea nd norepinephrineA. lso, we are gratefult o MICHAEL J. KUHAR for helpful discussioni n the final preparationo f this manuscript.
PY - 1975
Y1 - 1975
N2 - 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.
AB - 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.
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U2 - 10.1016/0028-3908(75)90026-X
DO - 10.1016/0028-3908(75)90026-X
M3 - Article
C2 - 1171389
AN - SCOPUS:0016745201
SN - 0028-3908
VL - 14
SP - 431
EP - 444
JO - Neuropharmacology
JF - Neuropharmacology
IS - 5-6
ER -