Alcohol addiction is a complicated disorder thought to involve an intersection of aspects of the individual, the environment, and alcohol itself. Stress/anxiety-related behaviors are an example of an interaction between the environment and the individual that may play a critical role in alcohol addiction. The bed nucleus of the stria terminalis (BNST) is a brain region thought to play a critical role, both in regulating stress and anxiety responses, and in mediating interactions between the stress and reward circuitries. A growing body of evidence suggests that this region may play a key role in aspects of stress-induced alcohol intake. We have found that NMDA receptor dependent synaptic plasticity can be evoked at glutamatergic synapses in this region, and that this plasticity, and NMDA receptor function itself, is regulated by acute ethanol administration. In this competing renewal, we aim to determine the mechanisms underlying the in vitro acute effects of ethanol in this brain region. In addition, we wish to understand what effects more behaviorally relevant chronic administration of ethanol to the whole animal has on BNST function. Finally, evidence suggests that 1) withdrawal from chronic administration of alcohol is associated with an increase in extracellular corticotrophin releasing factor (CRF) levels in the BNST, 2) alterations in CRF signaling alter alcohol drinking behavior, 3) CRF in the BNST is required for stress-induced reinstatement of psychostimulants, and 4) CRF regulates NMDA receptor function, and NMDA receptor-dependent synaptic plasticity in other brain regions. Thus, we will assess the effects of CRF receptor activation on glutamatergic synaptic transmission in the BNST. In total, the successful completion of these studies will advance our understanding of the mechanisms underlying the interactions of alcohol and anxiety centers, and set the stage for a screen for novel pharmaceutical and behavioral approaches to ameliorate stress/anxiety induced alcohol abuse.
