Altered central monoamine response to D-amphetamine in rats chronically exposed to inorganic lead.
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.
Lasley
S M
SM
Greenland
R D
RD
Minnema
D J
DJ
Michaelson
I A
IA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis*; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D015102:3,4-Dihydroxyphenylacetic Acid; D007854:Lead; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003913:Dextroamphetamine; D004298:Dopamine