Distinct patterns of neural activation associated with ethanol seeking: Effects of naltrexone
Distinct patterns of neural activation associated with ethanol seeking: Effects of naltrexone
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DOI：
10.1016/j.biopsych.2006.07.034
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发表时间：
2007-04-15
影响因子：
10.6
通讯作者：
Weiss, Friedbert
中科院分区：
文献类型：
--
作者：
Dayas, Christopher V.;Liu, Xiu;Weiss, Friedbert
背景：酒精中毒，像其他物质滥用障碍，是一种慢性复发性疾病。然而，与其他滥用药物相比，人们对乙醇（EtOH）渴求和寻求行为导致复吸的神经机制知之甚少。因此，进行本研究以识别由EtOH相关的上下文刺激（S+）招募的候选脑区域。第二个目的是确定是否EtOH S+-引起的神经募集模式被阿片拮抗剂纳洛酮（NTX）改变，纳洛酮是一种化合物，可以减少酗酒者的线索诱导的渴望，并减弱复发动物模型中的乙醇寻求。在复发的条件性恢复模型中测试大鼠，随后检查由EtOH S+引发的脑c-fos表达模式。与非奖赏（S-）相关的线索相比。结果：EtOH S+可使前额叶皮层、海马、丘脑背侧核、下丘脑室旁核（PVN）内c-fos表达恢复，并使c-fos表达增加。纳洛酮抑制S+诱导的恢复和衰减海马CA 3 c-fos的表达，同时增加神经活动的扩展杏仁核和PVN.Conclusions：乙醇相关的上下文刺激招募关键的大脑区域，调节联想学习，目标导向的行为，和巴甫洛夫条件反射的情感意义，以前中性的刺激。此外，这些数据暗示海马，杏仁核，PVN作为潜在的底物NTX的抑制作用条件性恢复。
Background: Alcoholism, like other substance abuse disorders, is a chronically relapsing condition. Compared with other abused drugs, however, little is known about the neural mechanisms mediating ethanol (EtOH)-craving and -seeking behavior leading to relapse. This study, therefore, was conducted to identify candidate brain regions that are recruited by an EtOH-associated contextual stimulus (S+). A secondary objective was to determine whether EtOH S+-elicited neural recruitment patterns are modified by the opiate antagonist naltrexone (NTX), a compound that reduces cue-induced craving in alcoholics and attenuates ethanol seeking in animal models of relapse.Methods: Rats were tested in a conditioned reinstatement model of relapse with subsequent examination of brain c-fos expression patterns elicited by an EtOH S+ versus a cue associated with nonreward (S-). In addition, modification of these expression patterns by NTX was examined.Results: The EtOH S+ reinstated extinguished responding and increased c-fos expression within the prefrontal cortex, hippocampus, nucleus accumbens, and hypothalamic paraventricular nucleus (PVN). Naltrexone suppressed the S+-induced reinstatement and attenuated hippocampal CA3 c-fos expression, while increasing neural activity in the extended amygdala and PVN.Conclusions: Ethanol-associated contextual stimuli recruit key brain regions that regulate associative learning, goal-directed behavior, and Pavlovian conditioning of emotional significance to previously neutral stimuli. In addition, the data implicate the hippocampus, amygdala, and PVN as potential substrates for the inhibitory effects of NTX on conditioned reinstatement.