Corticosterone down-regulates dopamine D4 receptor in a mouse cerebral cortex neuronal cell line

We have previously reported that restraint stress applied to the gestant mother results in long-lasting effects in the offspring that show an increase in the number of dopamine D-2-type receptors in limbic areas on the adult rat brain cortex. Evidence that stress during pregnancy results in activation of the hypothalamic-pituitary-adrenal (HPA) axis has been extensively demostrated. Therefore, high levels of corticosterone secreted in response to stress by the gestant mother might be one of the predisposing factors for the changes observed in dopamine receptors in the adult rat brain. In this study we addressed the question whether corticosterone would directly up-regulate D-2-type receptors in vitro. We have investigated the effect of different concentrations of corticosterone on D-4 dopamine receptor in immortalized cell lines from cerebral cortex of normal mouse fetuses, detected by immunocytochemistry employing polyclonal antibodies generated against synthetic peptides homologous to an extracellular domain of D-4 receptor. The results show that corticosterone in vitro decreases the number of dopamine D-4 receptors, suggesting that the increase of D-2-type receptors in adult rats following prenatal stress is not related to a direct action of corticosterone on receptor expression.