Investigations of the mechanisms involved in the neurotoxicity resulting from chronic inorganic lead (Pb) exposure have centered on CNS biogenic amine function on the basis of behavioral and neurochemical findings. The following study examined the time course of the response of dopamine (DA) and 5-hydroxytryptamine (5-HT) neurons to d-amphetamine (AMPH) in rats chronically exposed to Pb from birth in order to further examine neurochemical mechanisms implicated by previous work. Offspring were exposed to 0.2% Pb acetate via the lactating dam and then weaned to the same drinking solution. At 120–140 days animals were injected with 1.0 mg/kg s.c. of the drug or with saline and sacrificed after various intervals. DA content in nucleus accumbens and corpus striatum in Pb-exposed animals was significantly higher than corresponding levels in controls at 20 minutes post-drug and remained significantly higher than baseline values at 80 minutes after the drug when DA concentrations in controls had returned to normal. These data suggest enhanced AMPH-induced DA synthesis in exposed rats. 5-Hydroxyindoleacetic acid (5-HIAA) content was significantly increased in three brain regions in exposed rats given AMPH compared to values in saline-injected exposed animals, indicating a compensation in these areas for the decreases in 5-HIAA values produced by Pb exposure alone. The results of this study reinforce the hypothesis that DA and 5-HT neurons are sensitive to relatively low levels of Pb exposure.

The results of previous behavioral studies utilizing chronic exposure to low amounts of inorganic lead (Pb) have suggested alterations in the function of biogenic amine neuronal systems. The following study was performed to provide evidence for the possible bases of these changes in pharmacological responsiveness in exposed animals. Dams were administered 0.2% Pb acetate in drinking water to expose their offspring to Pb via the maternal milk. Males were weaned to the same drinking solution. At 120–140 days a tracer dose of 1.0 mCil-[3H]2,6-tyrosine (3H-TYR) and 0.5 mCil-[3H(G)]tryptophan (3H-TRP) was injected through an indwelling jugular catheter, and norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and their respective precursors and metabolites were quantified by liquid chromatography with electrochemical detection with column eluate collected for liquid scintillation counting. At this level of exposure (blood lead (PbB) at day 90 in exposed animals=43.1±1.7 μg/dl) no changes were observed in concentration Nf NE or DA mr DA metabolites in any brain region. However, DA turnover was decreased in Pb-exposed animals in nucleus accumbens and frontal cortex. No changes in 5-HT content and turnover were observed in any brain region, but 5-hydroxyindoleacetic acid (5-HIAA) levels were decreased in 6 of the 9 brain regions examined. These findings are consistent with observations of an attenuated behavioral responsiveness to d-amphetamine (AMPH) in exposed animals, and suggest that the changes in DA and 5-HT neurons noted by other workers at higher levels of exposure persist when PbBs are in the range of 40 μg/dl.

The determination of glutamic and gamma-aminobutyric acids in rat brain regions by derivatization with 0-phthaldialdehyde-thiol, isocratic separation by liquid chromatography, and quantification by electrochemical detection provides a simple and precise method for assessing changes in glutamatergic and GABAergic neuronal systems. Gamma-aminobutyric acid was eluted in 30–35 minutes followed by a washout step with 90% methanol to remove all amino acid derivatives with longer retention times. Homoserine was used as an internal standard. Significant increases in gamma-aminobutyric acid content in nucleus accumbens and substantia nigra could be detected 20 minutes after injection of 400 mg/kg valproic acid.

An automated technique for the study of visual discrimination learning in mice has been developed. The technique utilizes a nose-poke as the operant response. The nose-poke response requires no shaping, has a relatively high operant level and can be used to measure preacquisition exploratory behavior. CD-1 mice acquired a simultaneous brightness discrimination readily but a successive brightness discrimination proved more difficult. A 20 sec intertrial interval was optimal for acquisition of the simultaneous discrimination. Reversal learning was slow. This procedure should prove useful in the study of the effects of pharmacologic and toxic agents on learning and performance in both weanlings and adult mice.

An automated technique for the study of visual discrimination learning in mice has been developed. The technique utilizes a nose-poke as the operant response. The nose-poke response requires no shaping, has a relatively high operant level and can be used to measure preacquisition exploratory behavior. CD-1 mice acquired a simultaneous brightness discrimination readily but a successive brightness discrimination proved more difficult. A 20 sec intertrial interval was optimal for acquisition of the simultaneous discrimination. Reversal learning was slow. This procedure should prove useful in the study of the effects of pharmacologic and toxic agents on learning and performance in both weanlings and adult mice.

Lead poisoning was produced in suckling rats by lead fed to lactating mother rats being transmitted to newborns via maternal milk. The brain of 25 day old lead poisoned rats contained 6.0 to 12.5 ppm lead. Zinc was depressed 56% (cerebral cortex), 45% in cerebellum and 43% (caudate nucleus) whereas copper was depressed 52% in the cerebellum. Inhibition of monoamine oxidase (pargyline) or partial depletion of serotonin and norepinephrine did not alter the concentration of Fe, Cu, Zn, or Mn in brain.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of halogens on o-phthaldialdehyde-histamine and spermidine fluorescenceI. Arthur. Michaelson and Helen R. SmithsonCite this: Anal. Chem. 1971, 43, 10, 1300–1302Publication Date (Print):August 1, 1971Publication History Published online1 May 2002Published inissue 1 August 1971https://pubs.acs.org/doi/10.1021/ac60304a041https://doi.org/10.1021/ac60304a041research-articleACS PublicationsRequest reuse permissionsArticle Views71Altmetric-Citations5LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

The concentration of histamine and spermidine in fifteen different regions of rhesus monkey (Macaco mulatta) brain were studied using the O-phthaldialdehyde fluorometric method. The highest levels for histamine were found in the hypothalamus. Spermidine was found in all the regions studied and, unlike histamine, lacked significant regional localization within the central nervous system.

We have repeated our studies, ‡‡I.A. Michaelson and G.D. Dowe, Biochem. Pharmac.12, 949 (1963). with the O-phthalaldehyde (OPT) fluorescence method, §§P.A. Shore, A. Burkhalter and V.H. Cohn, J. Pharmac. exp. Ther.127, 182 (1959). of the subcellular distribution of histamine in guinea pig midbrain, this time purifying the extracts with cation-exchange resin chromatography. Our previous values included spermidine along with histamine. Guinea pig midbrain contains 0.55 nanomole histamine and 300 nanomoles spermidine. Histamine is bound to both a low-speed nuclear precipitate and an intermediate-speed mitochondrial precipitate. Forty-seven per cent of the spermidine is in the nuclear fraction. Attempts to relate histamine to subfractions of the mitochondrial fraction separated by density gradient centrifugation have been unsuccessful.

Annals of the New York Academy of SciencesVolume 144, Issue 2 p. 387-410 THE SUBCELLULAR DISTRIBUTION OF ACETYLCHOLINE, CHOLINE ACETYLTRANSFERASE AND ACETYL CHOLINESTERASE IN NERVE TISSUE I. Arthur Michaelson, I. Arthur Michaelson Department of Pharmacology, University of Cincinnati, College of Medicine Cincinnati, OhioSearch for more papers by this author I. Arthur Michaelson, I. Arthur Michaelson Department of Pharmacology, University of Cincinnati, College of Medicine Cincinnati, OhioSearch for more papers by this author First published: October 1967 https://doi.org/10.1111/j.1749-6632.1967.tb53784.xCitations: 27AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume144, Issue2Cholinergic MechanismaOctober 1967Pages 387-410 RelatedInformation

This paper reports a competitive solid-phase enzyme immunoassay for measuring histamine in various biological samples. In this assay, the histamine to be quantified is chemically modified by 1,4-benzoquinone treatment and allowed to compete with a histamine-peroxidase conjugate for binding to a limited amount of an anti-histamine monoclonal antibody which was used to coat the wells of a microtitration plate. After incubation and washing, peroxidase activity associated with the solid phase is measured. With this method the histamine concentration in blood or various tissues may be determined easily, safely and reproducibly. Histamine concentrations from 0.3 to 20 ng/ml may be measured with the procedure reported here.

The subcellular distribution of histamine has been analysed in guinea pig whole brain, dog hypothalamus and dog pituitary gland. In whole brain, histamine is found in both the nuclear and crude mitochondrial fractions. In brain tissue lacking mast cells (hypothalamus) “bound” histamine precipitates with the 17,000 g crude mitochondrial fraction, whereas 94 per cent of the “bound” histamine of the pituitary precipitates with the mast cells in the low speed nuclear fraction. Electron microscopic examination of subfractionated mitochondrial preparations from hypothalamus do not reveal structures comparable to the histamine containing granules of mast cells and a different type of histamine storage granule is suggested.

Studies of the biochemical effects of the thymine analog, 5-bromouracil (BU), on a thymine-requiring mutant of E. coli, were carried out. Partial inhibition of growth was noted within 30 min after the compound was added to an exponentially growing culture. With cultures grown to the same turbidity, the analog produced no effect on the utilization of the nucleic acid precursors, 2-14C-uracil and 4-14C-guanine, whereas that of 2-14C-thymine was blocked completely. Correspondingly, the content of RNA was identical when cells were grown to the same turbidity in the presence or absence of BU; on the other hand, the synthesis of DNA was only 25 per cent of that of the control, and cell division stopped entirely. During this period, BU continued to be incorporated into new DNA, but it did not displace the thymine already in DNA. Although the drug decreased the rate of protein synthesis for corresponding increases in cell mass, more protein synthesis took place in the BU-inhibited cultures, and certain amino acids were utilized to a still greater extent. The possibility of disruption in the normal process of protein synthesis is discussed.