[Exposure to bisphenol-A affects the rewarding system in mice].
Bisphenol-A has been extensively evaluated for toxicity in a variety of tests as the most common environmental endocrine disruptor. In the present study, we found that prenatal and neonatal exposure to bisphenol-A affects the development of the central dopaminergic system in the mouse limbic area. Additionally, this treatment with bisphenol-A produced a down-regulation of dopamine D3 receptor and an up-regulation of dopamine D1 receptor function to activate G-protein in the mouse limbic forebrain, which is thought to play a critical role for rewarding effects by drugs of abuse. We next investigated the relationship between the neurobehavioral toxicity and its exposure period. The exposure to bisphenol-A during either organogenesis or lactation, but not implantation and parturition, significantly enhanced the morphine-induced hyperlocomotion and rewarding effect. Furthermore, the exposure to bisphenol-A during either organogenesis or lactation also produced an up-regulation of dopamine D1 receptor function to activate G-protein in the mouse limbic forebrain. These results indicate that either organogenesis or lactation is more sensitive to the bisphenol-A-induced neuronal toxicity than any other periods. In conclusion, we found here that prenatal and neonatal exposure to bisphenol-A can potentiate the central dopaminergic systems, resulting in the supersensitivity of the drugs of abuse-induced rewarding effects and hyperlocomotion in the mouse. Furthermore, the organogenesis and lactation are the most important period to cause the alteration of dopaminergic system by bisphenol-A exposure in the mouse.
Suzuki
Tsutomu
T
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, Japan. suzuki@hoshi.ac.jp
Mizuo
Keisuke
K
Miyagawa
Kazuya
K
Narita
Minoru
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001559:Benzhydryl Compounds; D001921:Brain / Q000378:metabolism; D004357:Drug Synergism; D004703:Endocrine System / Q000187:drug effects; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D018811:Maternal Exposure / Q000009:adverse effects*; D008694:Methamphetamine / Q000009:adverse effects; D051379:Mice; D009020:Morphine / Q000009:adverse effects; D009043:Motor Activity / Q000187:drug effects; D010636:Phenols / Q000009:adverse effects*; D011247:Pregnancy; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050637:Receptors, Dopamine D3; D012201:Reward; D019966:Substance-Related Disorders / Q000209:etiology; D015854:Up-Regulation / Q000502:physiology; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D008694:Methamphetamine; D009020:Morphine; D010636:Phenols; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C493594:Drd3 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds