Ricerc@Sapienza

Although early aversive postnatal events are known to increase the risk to develop psychiatric disorders later in life, rarely they determine alone the nature and outcome of the psychopathology, indicating that interaction with genetic factors is crucial for expression of psychopathologies in adulthood. We have recently showed that Repeated Cross Fostering (RCF, Fig 1) experienced by pups affected the response to a negative experience in adulthood in opposite direction in two genotypes leading DBA2/J, but not C57BL/6J (C57) mice, toward an "anhedonic-like" phenotype. In contrast, individuals belonging to C57 strain, that appear to be resilient to develop an anhedonic-like behavioral phenotype, showed an increased sensitivity for a natural reinforcing stimulus, thus suggesting an enhanced response of the reward system to pharmacological stimuli (drugs of abuse).
Based on strong preliminary data, here we suggest that RCF makes C57 mice more prone to develop an addiction-like phenotype in adulthood by affecting genes expression in the NAc.
The main goal of this project will be to directly investigate the role of candidate genes in the addiction-like phenotype shown by RCF C57. We have till now selected two target genes, down regulated in our RCF model of "instability of the early environment" in C57 mice, and we plan, through an innovative technique based on adeno-associated virus gene therapy, to restore control levels of these genes' mRNA and check subsequent effects on the addiction-like phenotype. Moreover, pharmacological treatments will be tested to counteract deleterious effects of RCF experience in adulthood. Understanding and rescuing the mechanisms responsible for early stress-induced drug addiction-like phenotype in our RCF mouse model, could represent a first step to investigate other forms of addiction and explore the translational nature of our results.