A corticotropin releasing factor pathway for ethanol regulation of the ventral tegmental area in the bed nucleus of the stria terminalis.
A corticotropin releasing factor pathway for ethanol regulation of the ventral tegmental area in the bed nucleus of the stria terminalis.
复制标题
DOI：
10.1523/jneurosci.2949-12.2013
复制
发表时间：
2013-01-16
期刊：
影响因子：
--
通讯作者：
Winder DG
中科院分区：
文献类型：
--
作者：
Silberman Y;Matthews RT;Winder DG
A growing literature suggests that catecholamines and corticotropin releasing factor (CRF) interact in a serial manner to activate the bed nucleus of the stria terminalis (BNST) in order to drive stress- or cue-induced drug- and alcohol-seeking behaviors. Data suggests that these behaviors are driven in part by BNST projections to the ventral tegmental area (VTA). Together these findings suggest the existence of a CRF-signaling pathway within the BNST that is engaged by catecholamines and regulates the activity of BNST neurons projecting to the VTA. Here we test three aspects of this model: 1) whether catecholamines modify CRF neuron activity in the BNST, 2) whether CRF regulates excitatory drive onto VTA-projecting BNST neurons, and 3) whether this system is altered by ethanol exposure and withdrawal. A CRF neuron fluorescent reporter strategy was utilized to identify BNST CRF neurons for whole cell patch clamp analysis in acutely prepared slices. Using this approach, we found that both dopamine and isoproterenol significantly depolarized BNST CRF neurons. Furthermore, using a fluorescent microsphere based identification strategy; we found that CRF enhances the frequency of spontaneous EPSCs onto VTA-projecting BNST neurons in naïve mice. This action of CRF was occluded during acute withdrawal from chronic intermittent ethanol exposure. These findings suggest that dopamine and isoproterenol may enhance CRF release from local BNST sources, leading to enhancement of excitatory neurotransmission on VTA-projecting neurons, and that this pathway is engaged by patterns of alcohol exposure and withdrawal known to drive excessive alcohol intake.
