TY - JOUR T1 - Early Social Isolation Stress and Perinatal NMDA Receptor Antagonist Treatment Induce Changes in the Structure and Neurochemistry of Inhibitory Neurons of the Adult Amygdala and Prefrontal Cortex JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0034-17.2017 VL - 4 IS - 2 SP - ENEURO.0034-17.2017 AU - Esther Castillo-Gómez AU - Marta Pérez-Rando AU - María Bellés AU - Javier Gilabert-Juan AU - José Vicente Llorens AU - Héctor Carceller AU - Clara Bueno-Fernández AU - Clara García-Mompó AU - Beatriz Ripoll-Martínez AU - Yasmina Curto AU - Noelia Sebastiá-Ortega AU - María Dolores Moltó AU - Julio Sanjuan AU - Juan Nacher Y1 - 2017/03/01 UR - http://www.eneuro.org/content/4/2/ENEURO.0034-17.2017.abstract N2 - The exposure to aversive experiences during early life influences brain development and leads to altered behavior. Moreover, the combination of these experiences with subtle alterations in neurodevelopment may contribute to the emergence of psychiatric disorders, such as schizophrenia. Recent hypotheses suggest that imbalances between excitatory and inhibitory (E/I) neurotransmission, especially in the prefrontal cortex and the amygdala, may underlie their etiopathology. In order to understand better the neurobiological bases of these alterations, we studied the impact of altered neurodevelopment and chronic early-life stress on these two brain regions. Transgenic mice displaying fluorescent excitatory and inhibitory neurons, received a single injection of MK801 (NMDAR antagonist) or vehicle solution at postnatal day 7 and/or were socially isolated from the age of weaning until adulthood (3 months old). We found that anxiety-related behavior, brain volume, neuronal structure, and the expression of molecules related to plasticity and E/I neurotransmission in adult mice were importantly affected by early-life stress. Interestingly, many of these effects were potentiated when the stress paradigm was applied to mice perinatally injected with MK801 ("double-hit" model). These results clearly show the impact of early-life stress on the adult brain, especially on the structure and plasticity of inhibitory networks, and highlight the double-hit model as a valuable tool to study the contribution of early-life stress in the emergence of neurodevelopmental psychiatric disorders, such as schizophrenia. ER -