Learning Modulate Down Regulation of GABA_Aα1 Receptors in Amygdala and Cerebellum of Rats Exposed to Bisphenol A

Background: Bisphenol A (BPA) has been acknowledged as an estrogenic chemical able to interact with estrogen receptors. Bisphenol A at high concentration inhibited the GABA_Aα1 receptor mediated response. Objectives: The study was conducted to investigate the effect of BPA on GABA_Aα1 receptors density in amygdala and cerebellum of adult rats and the possible modulatory effect of passive avoidance learning. Methods: Thirty male Sprague-Dawley rats weighting 200 to 220 g were used. Bisphenol A 5 and 50 mg kg^-1 day^-1 were administrated by oral intake for 15 days. Learning and memory tasks were performed by shuttle-box. Densities of GABA_Aα1receptor were investigated by immunohistochemical procedure. Results: Rats with learning had significantly higher GABA_Aα1 receptor ascomparedto control rats. The administration of BPAat both low and high doses significantly reduced receptor density in a dose-dependent manner in comparison with control rats. Learning significantly increased receptor density in rats treated with BPA as compared to unlearned BPA treated rats, however, it could not completely reverse this parameter and these rats still had lower receptor density than controls. Conclusions: In conclusion, BPA induces dose-dependent down-regulation of GABA_Aα1 receptors in the amygdala and Purkinje cell layer of cerebellum of adult rats, which could be partially compensated by learning.