Effects of lifelong dietary exposure to genistein or nonylphenol on amphetamine-stimulated striatal dopamine release in male and female rats.
Estrogen modulates baseline and amphetamine-stimulated dopamine (DA) release in the adult female rat striatum. The isoflavone found in soybeans, genistein, is a phytoestrogen and may have comparable effects on striatal DA levels. Similarly, the industrial intermediate and potential endocrine disrupter, para-nonylphenol, has estrogen-like effects. Here, Sprague-Dawley rats were continuously exposed to phytoestrogen-free diets containing 0, 100, or 500 ppm genistein (Experiment 1) or 0 or 200, or 750 ppm nonylphenol (Experiment 2) beginning at conception and continuing throughout. To eliminate estrous cycle influences on DA levels, females were ovariectomized at adulthood. As adults, striatal levels of DA and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were measured in unanesthetized male and female rats via cerebral microdialysis before and for 200 min after an intraperitoneal injection of 2 mg/kg D-amphetamine. Although baseline 5-hydroxyindoleacetic acid (5-HIAA) levels indicated an isolated effect in genistein-treated females, there were no meaningful differences among treatment groups in baseline levels of DA, DOPAC, or HVA. However, dietary exposure to 500 ppm genistein significantly potentiated amphetamine-stimulated DA release in males and a similar trend was apparent, but not statistically significant, in females. Dietary exposure to 200 or 750 ppm nonylphenol had no significant effects in males or females. These results suggest that dietary genistein exposure may act similarly to estradiol in augmenting amphetamine-stimulated DA release.
Ferguson
Sherry A
SA
Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Road, HFT-132, Jefferson, AR 72079, USA. sferguson@nctr.fda.gov
Flynn
Katherine M
KM
Delclos
K Barry
KB
Newbold
Retha R
RR
Gough
Bobby J
BJ
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004032:Diet; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000819:agonists*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D010052:Ovariectomy; D010636:Phenols / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D018765:Dopamine Uptake Inhibitors; D004967:Estrogens; D010636:Phenols; C025256:nonylphenol; D000661:Amphetamine; D019833:Genistein; D004298:Dopamine