Behavioral alterations in response to fear-provoking stimuli and tranylcypromine induced by perinatal exposure to bisphenol A and nonylphenol in male rats.
The purpose of this study was to examine whether perinatal exposure to two major environmental endocrine-disrupting chemicals, bisphenol A (BPA; 0.1 mg/kg/day orally) and nonylphenol [NP; 0.1 mg/kg/day (low dose) and 10 mg/kg/day (high dose) orally] daily from gestational day 3 to postnatal day 20 (transplacental and lactational exposures) would lead to behavioral alterations in the male offspring of F344 rats. Neither BPA nor NP exposure affected behavioral characteristics in an open-field test (8 weeks of age), in a measurement of spontaneous motor activity (12 weeks of age), or in an elevated plus-maze test (14 weeks of age). A passive avoidance test (13 weeks of age) showed that both BPA- and NP-treated offspring tended to delay entry into a dark compartment. An active avoidance test at 15 weeks of age revealed that BPA-treated offspring showed significantly fewer avoidance responses and low-dose NP-treated offspring exhibited slightly fewer avoidance responses. Furthermore, BPA-treated offspring significantly increased the number of failures to avoid electrical unconditioned stimuli within 5-sec electrical shock presentation compared with the control offspring. In a monoamine-disruption test using 5 mg/kg (intraperitoneal) tranylcypromine (Tcy), a monoamine oxidase inhibitor, both BPA-treated and low-dose NP-treated offspring at 22-24 weeks of age failed to show a significant increment in locomotion in response to Tcy, whereas control and high-dose NP-treated offspring significantly increased locomotion behavior after Tcy injection. In addition, when only saline was injected during a monoamine-disruption test, low-dose NP-treated offspring showed frequent rearing compared with the control offspring. The present results indicate that perinatal low-dose BPA or NP exposure irreversibly influenced the reception of fear-provoking stimuli (e.g., electrical shock), as well as monoaminergic neural pathways. Key words: behavior, bisphenol A, fear, learning, monoamine, nonylphenol.
Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. taka-u@yayoi.club.ne.jp
Takayuki
T
Negishi
Katsuyoshi
K
Kawasaki
Shingo
S
Suzaki
Haruna
H
Maeda
Yoshiyuki
Y
Ishii
Shigeru
S
Kyuwa
Yoichiro
Y
Kuroda
Yasuhiro
Y
Yoshikawa
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005239:Fear; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011916:Rats, Inbred F344; D014191:Tranylcypromine / Q000008:administration & dosage / Q000494:pharmacology; D000098826:Bisphenol A Compounds
D014151:Anti-Anxiety Agents; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D014191:Tranylcypromine; C025256:nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds