Neonatal overexpression of estrogen receptor- alters midbrain dopamine neuron development and reverses the effects of low maternal care in female offspring

摘要

Maternal behavior is dependent on estrogen receptor-alpha (ER; Esr1) and oxytocin receptor (OTR) signaling in the medial preoptic area (MPOA) of the hypothalamus, as well as dopamine signaling from the ventral tegmental area (VTA) to forebrain regions. Previous studies in rats indicate that low levels of maternal care, particularly licking/grooming (LG), lead to reduced levels of MPOA ER and VTA dopamine neurons in female offspring and predict lower levels of postpartum maternal behavior by these offspring. The aim of this study was to determine the functional impact on maternal behavior of neonatal manipulation of ER in females that had experienced low versus high levels of postnatal maternal LG. Adenovirus expressing ESR1 was targeted to the MPOA in female pups from low and high LG litters on postnatal day 2-3. Overexpression of ESR1 in low LG offspring elevated the level of ER-immunoreactive cells in the MPOA and of tyrosine hydroxylase cells in the VTA to that observed in high LG females. Amongst juvenile female low LG offspring, ESR1 overexpression also decreased the latency to engage in maternal behavior toward donor pups. These results show that virally mediated expression of ESR1 in the neonatal rat hypothalamus results in lasting changes in ESR1 expression through the juvenile period, and can rescue hormone receptor levels and behavior of offspring reared by low LG dams, potentially mediated by downstream alterations within reward circuitry. Thus, the transmission of maternal behavior from one generation to the next can be augmented by neonatal ER in the MPOA. (c) 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 1114-1124, 2015