Camarini Rosana, Pautassi Ricardo Marcos
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil.
Instituto de Investigaciones Médicas M. y M. Ferreyra, Córdoba (IMMF-CONICET-Universidad Nacional de Córdoba), Universidad Nacional de Córdoba, Argentina.
Brain Res Bull. 2016 Jul;125:53-78. doi: 10.1016/j.brainresbull.2016.04.006. Epub 2016 Apr 16.
Ethanol-induced behavioral sensitization (EBS) was first described in 1980, approximately 10 years after the phenomenon was described for psychostimulants. Ethanol acts on γ-aminobutyric acid (GABA) and glutamate receptors as an allosteric agonist and antagonist, respectively, but it also affects many other molecular targets. The multiplicity of factors involved in the behavioral and neurochemical effects of ethanol and the ensuing complexity may explain much of the apparent disparate results, found across different labs, regarding ethanol-induced behavioral sensitization. Although the mesocorticolimbic dopamine system plays an important role in EBS, we provide evidence of the involvement of other neurotransmitter systems, mainly the glutamatergic, GABAergic, and opioidergic systems. This review also analyses the neural underpinnings (e.g., induction of cellular transcription factors such as cyclic adenosine monophosphate response element binding protein and growth factors, such as the brain-derived neurotrophic factor) and other factors that influence the phenomenon, including age, sex, dose, and protocols of drug administration. One of the reasons that make EBS an attractive phenomenon is the assumption, firmly based on empirical evidence, that EBS and addiction-related processes have common molecular and neural basis. Therefore, EBS has been used as a model of addiction processes. We discuss the association between different measures of ethanol-induced reward and EBS. Parallels between the pharmacological basis of EBS and acute motor effects of ethanol are also discussed.
乙醇诱导的行为敏化（EBS）于1980年首次被描述，这一现象在精神兴奋剂领域被描述大约10年后。乙醇分别作为变构激动剂和拮抗剂作用于γ-氨基丁酸（GABA）和谷氨酸受体，但它也会影响许多其他分子靶点。乙醇行为和神经化学效应所涉及的多种因素以及随之而来的复杂性，可能解释了不同实验室在乙醇诱导的行为敏化方面所发现的许多明显不同的结果。尽管中脑边缘多巴胺系统在EBS中起重要作用，但我们提供了其他神经递质系统参与的证据，主要是谷氨酸能、GABA能和阿片样物质能系统。本综述还分析了神经基础（如细胞转录因子如环磷酸腺苷反应元件结合蛋白的诱导和生长因子如脑源性神经营养因子）以及影响该现象的其他因素，包括年龄、性别、剂量和药物给药方案。使EBS成为一个有吸引力的现象的原因之一是基于经验证据的假设，即EBS与成瘾相关过程有共同的分子和神经基础。因此，EBS已被用作成瘾过程的模型。我们讨论了乙醇诱导的奖赏的不同测量方法与EBS之间的关联。还讨论了EBS的药理学基础与乙醇急性运动效应之间的相似之处。
