[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.