Childhood trauma confers vulnerability to comorbid PTSD/AUD, particularly in female patients. Because
the neural substrates mediating vulnerability to PTSD and AUD may be similar, elucidating these common
mechanisms may provide the foundation for novel treatment options for both. Infant trauma is a powerful,
construct-valid model of PTSD and AUD. Trauma-exposed animals show potentiated fear learning, resistance
to extinction, and increased alcohol drinking as adults and there is an enhanced vulnerability to these effects in
females. This proposal explores the novel hypothesis that infant trauma produces enduring upregulation in
MOR expression in amygdala intercalated neurons, ultimately disinhibiting neurons of the central amygdala.
Our experiments will test this hypothesis through completion of three primary specific aims. In male and female
mice, we will 1) determine whether MOR mRNA expression is increased in amygdala intercalated neurons
following infant trauma 2) identify novel molecular targets in the ITC that are regulated by stress and alcohol,
and 3) demonstrate a causal role for intercalated cells MORs in mediating the effects of infant trauma on
alcohol drinking. Infant trauma will be modeled by delivering 15 footshocks on postnatal day 17. Alcohol
drinking will be assessed in a two-bottle choice, drinking in the dark paradigm. Collectively, completion of these
aims will provide support for a mechanism by which early life adversity may increase sensitivity to stressors
and increase drinking in adulthood. Our work will also further validate a model of traumatic stress and sex-
dependent effects on alcohol drinking.