期刊
JOURNAL OF NEUROSCIENCE
卷 29, 期 20, 页码 6535-6544出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4773-08.2009
关键词
-
资金
- National Institute on Drug Abuse [RO1 A016782]
- state of California for medical research on alcohol and substance abuse through the University of California, San Francisco
Current concepts suggest that stress-induced release of neuromodulators such as corticotropin-releasing factor (CRF) can drive drug-dependent behaviors. Although previous drug exposure can enhance behavioral and neurochemical responses to stress, it is unclear how such drug exposure alters the CRF modulation of excitatory synapses onto ventral tegmental area (VTA) dopamine neurons, a key locus of drug-and stress-induced neuroadaptation. Here, we demonstrate that, after repeated cocaine exposure, the magnitude and duration of the CRF-induced potentiation of NMDA receptor (NMDAR)-mediated neurotransmission was significantly increased compared with naive and saline-treated mice. Furthermore, CRF enhanced AMPA receptor (AMPAR)-mediated transmission only in mice that were exposed to cocaine. Increased frequency of AMPAR-mediated spontaneous miniature EPSCs and the intracellular blockade of CRF potentiation of AMPAR-mediated transmission suggest both presynaptic and postsynaptic effects of CRF. Importantly, pharmacological experiments revealed that CRF receptor 1 and protein kinase A pathways were newly recruited after repeated cocaine for the enhancement of CRF-induced NMDAR potentiation and the appearance of AMPAR potentiation. Thus, enhanced CRF-induced potentiation of excitatory synaptic transmission onto VTA dopamine neurons after cocaine preexposure is likely to produce an abnormal increase in dopamine release during stressful events and could augment activation of addictive behaviors in response to stress.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据