Effects of in utero and lactational exposure of the laboratory rat to 2,4,2',4'- and 3,4,3',4'-tetrachlorobiphenyl on dopamine function.
Offspring of Sprague-Dawley derived dams were exposed to either 2,4, 2',4'-tetrachlorobiphenyl (TCB) (1, 10, or 20 mg/(kg.day)) or 3,4,3', 4'-TCB (0.1 or 1 mg/(kg.day)) from gestational Day 6 through weaning by providing the dams with cookies adulterated with the appropriate amount and type of PCB. Male and female offspring were sacrificed on postnatal Days 35, 60, and 90, and brain concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were determined in the frontal cortex, caudate nucleus and substantia nigra by high-performance liquid chromatography with electrochemical detection. In utero and lactational exposure to 3,4,3',4'-TCB resulted in significant elevations in concentrations of dopamine in the frontal cortex, and of dopamine and its metabolites in the substantia nigra that persisted into adulthood. In contrast, in utero and lactational exposure to 2,4,2',4'-TCB resulted in significant decreases in concentrations of dopamine in the frontal cortex and caudate nucleus that also persisted into adulthood. We suggest that the reductions in brain dopamine concentrations are a consequence of ortho-substituted PCB congener-induced inhibition of the synthesis of dopamine during critical periods of development acting, perhaps, in concert with PCB-induced changes in cholinergic receptor function. On the other hand, the persistent elevations in brain dopamine and metabolite concentrations following perinatal exposure to 3,4,3',4'-TCB may be mediated by alterations in steroid hormone function during key developmental periods.
Seegal
R F
RF
New York State Department of Health, University at Albany, Albany, New York 12201-0509, USA.
Brosch
K O
KO
Okoniewski
R J
RJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006719:Homovanillic Acid / Q000032:analysis; D007774:Lactation; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats
D015102:3,4-Dihydroxyphenylacetic Acid; C035976:2,4,2',4'-tetrachlorobiphenyl; D011078:Polychlorinated Biphenyls; D004298:Dopamine; D006719:Homovanillic Acid; C028451:3,4,3',4'-tetrachlorobiphenyl