Alcohol addiction is a complex disorder, in which the risk of abuse can be enhanced by stress and anxiety. A recurring theme in the study of stress and anxiety is the involvement of the neuropeptides corticotrophin releasing factor (CRF) and neuropeptide Y (NPY). Furthermore, it has been proposed that a dysregulation of both CRF and NPY play a critical role in the long lasting changes during alcohol abuse. One brain region with enriched expression of both CRF and CRF receptors (CRFRs) and NPY and NPY receptors (YRs) that has been previously shown to be regulated by ethanol exposure is the bed nucleus of the stria terminalis (BNST). A component of the """"""""extended amygdala"""""""", the BNST is uniquely situated to integrate stress- and reward-related processing in the CNS, regulating both CRF release from the PVN and activation of reward circuits. I will determine the effects of CRF (Aim 1) and NPY (Aim 2) on inhibitory synaptic transmission in the BNST in order to test the hypothesis that modulation of transmission is involved in alcohol abuse. Furthermore, I will examine synaptic inhibition in the BNST following of chronic ethanol withdrawal, to test the hypothesis that excitability in this region is altered in this anxiogenic state (Aim 3). ? ?
| Silberman, Yuval; Bajo, Michal; Chappell, Ann M et al. (2009) Neurobiological mechanisms contributing to alcohol-stress-anxiety interactions. Alcohol 43:509-19 |
| Kash, Thomas L; Baucum 2nd, Anthony J; Conrad, Kelly L et al. (2009) Alcohol exposure alters NMDAR function in the bed nucleus of the stria terminalis. Neuropsychopharmacology 34:2420-9 |
| Kash, Thomas L; Matthews, Robert T; Winder, Danny G (2008) Alcohol inhibits NR2B-containing NMDA receptors in the ventral bed nucleus of the stria terminalis. Neuropsychopharmacology 33:1379-90 |
| Kash, Thomas L; Nobis, William P; Matthews, Robert T et al. (2008) Dopamine enhances fast excitatory synaptic transmission in the extended amygdala by a CRF-R1-dependent process. J Neurosci 28:13856-65 |
| Healey, Julie C; Winder, Danny G; Kash, Thomas L (2008) Chronic ethanol exposure leads to divergent control of dopaminergic synapses in distinct target regions. Alcohol 42:179-90 |
