This thesis will study the effects of social defeat stress on the escalation of alcohol consumption as it relates to the paraventricular thalamus (PVT) and paraventricular nucleus of the hypothalamus (PVN). Psychosocial stressors are a significant risk factor for the development of various neuropsychiatric illnesses including addiction. It has been shown that those who consume alcohol in response to negative social experiences are more likely to meet the diagnostic criteria for alcohol use disorder in the Diagnostic and Statistical Manual (DSM-V) (1). Exposure to psychosocial stressors induces "loss of control"-type drinking in those who drink alcohol as a coping mechanism. Previous work from our lab show that social defeat stress (SDS) induced an escalation of alcohol consumption and enhanced preference for alcohol in both male and female C57BL/6J mice. Using a recombinant mouse that allows genetic access to transiently activated population of neurons (2), we identified a discrete population of neurons in the PVT and PVN that is strongly activated by SDS. We also found that in mice subject to SDS, the PVT and PVN are strongly activated by alcohol consumption. Further, there is a large overlap between cells that are activated by SDS and those that are activated by alcohol in both of these brain regions. We decided to focus on the PVT as it receives arousal-related inputs from a variety of brain regions and conveys them to limbic regions to direct motivated behaviors including drug seeking and taking. We hypothesize that cells activated by social defeats stress in the PVT and PVN drive escalated alcohol consumption. Using RNA in situ hybridization and viral-mediated tract tracing, we have further characterized the neurochemical identity as well as downstream projection targets of cells activated by SDS in the PVT. Future studies will establish causal relationships between activated cell populations and stress-escalated drinking.
