Influence of chronic inorganic lead exposure on regional dopamine and 5-hydroxytryptamine turnover in rat brain.
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 mCi L-[3H]2,6-tyrosine (3H-TYR) and 0.5 mCi L-[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 micrograms/dl) no changes were observed in concentration of NE or DA or 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 micrograms/dl.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000503:physiopathology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009647:Normetanephrine / Q000378:metabolism; D011247:Pregnancy; D011524:Protoporphyrins / Q000097:blood; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D011524:Protoporphyrins; D009647:Normetanephrine; D015102:3,4-Dihydroxyphenylacetic Acid; D007854:Lead; D012701:Serotonin; D014443:Tyrosine; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid