Early life adversity increases striatal density of dopamine D1 receptors and promotes social alcohol drinking in mice, especially males

Data and code for the publication entitled "Early life adversity increases striatal density of dopamine D1 receptors and promotes social alcohol drinking in mice, especially males "

The brain’s reward circuitry remains sensitive to experience throughout early life and into adulthood, allowing individuals to adapt to their unique environment. Adverse experiences early in life can increase vulnerability to substance use disorders, likely through alterations to this circuitry. Yet, the precise neurobiological mechanisms by which early life adversity acts are incompletely characterized. In this study, we used a limited bedding and nesting (LBN) paradigm as a translationally relevant model of early life adversity in genetically-identical, C57BL/6J mice. We assessed the lasting behavioral and mechanistic impacts of LBN experience in adulthood. A history of LBN-rearing demonstrated increased risk avoidance, enhanced acute response to alcohol, and greater voluntary alcohol drinking in socially-housed LBN-reared mice, especially males. Further, using autoradiography, we found LBN-reared mice had increased striatal D1-like receptor binding, skewing D1- to D2-like receptor balance relative to cross-fostered controls. However, after voluntary alcohol drinking, we found a strong downregulation in D1-like, and some D2-like, receptor binding, negating pre-existing differences in striatal dopamine receptor binding. We posit that via both transcriptional and post-transcriptional mechanisms, LBN-rearing upregulates striatal D1-receptor density and alters risk avoidance and acute alcohol stimulation to promote alcohol drinking among adversity-exposed mice. Together, these findings reveal specific neurobiological mechanisms that promote alcohol consumption following early life adversity and suggest complex interactions between early life adversity, sex-related factors, and dopamine receptor regulation in contributing to alcohol use disorder (AUD) vulnerability.