| Behavioral Alterations in Response to Fear-Provoking Stimuli and Tranylcypromine Induced by Perinatal Exposure to Bisphenol A and Nonylphenol in Male Rats Takayuki Negishi,1,2 Katsuyoshi Kawasaki,2,3 Shingo Suzaki,1 Haruna Maeda,1 Yoshiyuki Ishii,1 Shigeru Kyuwa,1 Yoichiro Kuroda,2,4 and Yasuhiro Yoshikawa1,2 1Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan; 2Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan; 3Department of Psychology, Hoshi University, Tokyo, Japan; 4Department of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan Abstract
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. Environ Health Perspect 112:1159-1164 (2004) . doi:10.1289/ehp.6961 available via http://dx.doi.org/ [Online 26 May 2004]
Address correspondence to T. Negishi, Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Telephone: 81-3-5841-5037. Fax. 81-3-5841-8186. E-mail: taka-u@yayoi.club.ne.jp The authors declare they have no competing financial interests. Received 12 January 2004 ; accepted 26 May 2004.
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