Chronic oral administration of MPEP, an antagonist of mGlu 5 receptor, during gestation and lactation alters mGlu 5 and A 2A receptors in maternal and neonatal brain.

Antidepressant and anxiolytic drugs are widely consumed even by pregnant and lactating women. The metabotropic glutamate receptor 5 (mGlu5 ) antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) exerts antidepressant- and anxiolytic-like actions. Given that treatment for anxiety and depression use to be prolonged in time, it is conceivable a possible modulation of metabotropic glutamate receptors (mGlu receptors) after prolonged MPEP exposure, which could also modify adenosine A2A receptors (A2A R) since functional cross-talk between them has been reported. Here we report that MPEP crosses placental barrier and reaches neonatal brain through maternal milk using LC-MS/MS methods. Therefore, we analyzed mGlu receptors, mainly mGlu5 , and A2A R in both maternal and fetal brain after chronic maternal consumption of MPEP during gestation and/or lactation using radioligand binding, Western-blotting, real-time PCR and phospholipase C (PLC) activity assays. In maternal brain, chronic MPEP consumption caused a significant loss of mGlu, including mGlu5 , and A2A R receptors level in plasma membrane. PLC activity assays showed that mGlu5 signaling pathway was desensitized. No variations on mRNA level coding A2A R, A1 R and mGlu5 were found after MPEP treatments. In female neonatal brain, maternal consumption of MPEP caused a significant increase in mGlu, including mGlu5 , and A2A R receptors level. Neither mGlu receptors nor A2A R were modified in male neonatal brain after maternal MPEP intake. Finally, neither molecular nor behavioral changes (anxiety- and depression-like behavior) were observed in 3-month-old female offspring. In summary, mGlu5 and A2A R are altered in both maternal and female neonatal brain after chronic maternal consumption of MPEP during gestation and/or lactation.