The role of serotonin signaling in the nucleus accumbens in excessive alcohol drinking

PROJECT SUMMARY/ABSTRACTNeurological complications of SARS-CoV2 or Covid-19 have been reported in the literature but little is knownabout the extent to which neural systems are affected by this disease or the long-term impact on brain function.Alcohol consumption during the Covid-19 pandemic is on the rise due to factors such as unemployment, financialstrain, and loss of social support and may be a significant risk factor for neurological complications of SARS-CoV2. Other coronaviruses such as SARS-CoV are thought to gain entry to the brain via the olfactory bulb andquickly spread to interconnected regions such as the dorsal raphe nucleus (DRN), which is a major source ofserotonin (5-HT) neurons in the brain that orchestrates neurological functions ranging from autonomic control toemotional and motivated behavior. Alcohol is also known to compromise the function of 5-HT neurons in thebrain and may render them more vulnerable to infection by SARS-CoV2, exacerbating the neuropsychiatricsequelae of this disease. The goal of the present application is to determine whether alcohol can increaseexpression of known entry factors for SARS-CoV2 in DRN 5-HT neurons and facilitate infection of these neurons.In Aim 1, we will determine whether chronic intermittent alcohol exposure upregulates expression of entry factorsACE2 and TMPRSS2 in 5-HT DRN neurons that project to the olfactory bulb using retrograde tracers. In Aim 2,we will determine whether SARS-CoV2 can infect 5-HT DRN neurons via the olfactory bulb and whether chronicintermittent alcohol exacerbates infection and death of these neurons. Together, these studies will revealwhether alcohol is a significant risk factor for SARS-CoV2 invasion of the CNS and whether the DRN 5-HTsystems is a target for this infection.