Neurocircuitry targets in ethanol reward and dependence
Neurocircuitry targets in ethanol reward and dependence
复制标题
DOI：
10.1111/j.1530-0277.1998.tb03611.x
复制
发表时间：
1998-02-01
期刊：
影响因子：
--
通讯作者：
Weiss, F
中科院分区：
文献类型：
--
作者：
Koob, GF;Roberts, AJ;Weiss, F
酗酒是一种复杂的行为障碍，其特征是过度消费乙醇、向过度消费方向缩小行为范围、产生耐受性和依赖性以及社会和职业功能受损。建立完整的酒精中毒综合症的动物模型即使不是不可能，也是很困难的，但针对该综合症的许多不同组成部分都存在经过验证的动物模型。最近的工作已经开始定义负责过量乙醇摄入动物模型关键的两个主要强化来源的神经回路：正强化和负强化。乙醇似乎与神经元膜内的乙醇敏感元件相互作用，从而传达神经化学作用的特异性。乙醇强化似乎是通过 GABA-A 受体的激活、阿片肽的释放、多巴胺的释放、谷氨酸受体的抑制以及与血清素系统的相互作用介导的。这些神经回路可能会因长期服用乙醇而改变，如急性乙醇戒断期间的相反作用以及其他神经递质系统（如应激神经肽促肾上腺皮质激素释放因子）的募集所反映的。未来的挑战将包括重点了解这些神经适应性变化如何使有乙醇依赖史的动物容易复发。
Alcoholism is a complex behavioral disorder characterized by excessive consumption of ethanol, a narrowing of the behavioral repertoire toward excessive consumption, the development of tolerance and dependence, and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome. Recent work has begun to define the neurocircuits responsible for the two major sources of reinforcement key to animal models of excessive ethanol intake: positive and negative reinforcement. Ethanol appears to interact with ethanol-sensitive elements within neuronal membranes that convey the specificity of neurochemical action. Ethanol reinforcement appears to be mediated by an activation of GABA-A receptors, release of opioid peptides, release of dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic ethanol administration as reflected by opposite effects during acute ethanol withdrawal and by the recruitment of other neurotransmitter systems such as the stress neuropeptide corticotropin-releasing factor. Future challenges will include a focus on understanding how these neuroadaptive changes convey vulnerability to relapse in animals with a history of ethanol dependence.