Miquel Marta, Toledo Rebeca, García Luis I, Coria-Avila Genaro A, Manzo Jorge
Area de Psicobiología, Universidad Jaume I, Castellón, Spain.
Curr Drug Abuse Rev. 2009 Jan;2(1):26-40. doi: 10.2174/1874473710902010026.
Increasing evidence has involved the cerebellum in functions beyond the sphere of motor control. In the present article, we review evidence that involves the cerebellum in addictive behaviour. We aimed on molecular and cellular targets in the cerebellum where addictive drugs can act and induce mechanisms of neuroplasticity that may contribute to the development of an addictive pattern of behaviour. Also, we analyzed the behavioural consequences of repetitive drug administration that result from activity-dependent changes in the efficacy of cerebellar synapses. Revised research involves the cerebellum in drug-induced long-term memory, drug-induced sensitization and the perseverative behavioural phenotype. Results agree to relevant participation of the cerebellum in the functional systems underlying drug addiction. The molecular and cellular actions of addictive drugs in the cerebellum involve long-term adaptative changes in receptors, neurotransmitters and intracellular signalling transduction pathways that may lead to the re-organization of cerebellar microzones and in turn to functional networks where the cerebellum is an important nodal structure. We propose that drug induced activity-dependent synaptic changes in the cerebellum are crucial to the transition from a pattern of recreational drug taking to the compulsive behavioural phenotype. Functional and structural modifications produced by drugs in the cerebellum may enhance the susceptibility of fronto-cerebellar circuitry to be changed by repeated drug exposure. As a part of this functional reorganization, drug-induced cerebellar hyper-responsiveness appears to be central to reducing the influence of executive control of the prefrontal cortex on behaviour and aiding the transition to an automatic mode of control.
越来越多的证据表明，小脑所涉及的功能超出了运动控制范围。在本文中，我们综述了小脑与成瘾行为相关的证据。我们着眼于小脑中成瘾药物能够作用并诱导神经可塑性机制的分子和细胞靶点，这些机制可能导致成瘾行为模式的形成。此外，我们分析了重复给药所产生的行为后果，这些后果源于小脑突触效能的活动依赖性变化。最新研究表明，小脑参与药物诱导的长期记忆、药物诱导的敏化作用以及持续性行为表型。结果表明小脑确实参与了成瘾背后的功能系统。成瘾药物在小脑中的分子和细胞作用涉及受体、神经递质和细胞内信号转导通路的长期适应性变化，这可能导致小脑微区的重新组织，进而形成以小脑为重要节点结构的功能网络。我们认为，药物诱导的小脑活动依赖性突触变化对于从娱乐性用药模式转变为强迫性的行为表型至关重要。药物在小脑中产生的功能和结构改变可能会增强额小脑回路对反复药物暴露的易感性。作为这种功能重组的一部分，药物诱导的小脑高反应性似乎对于减少前额叶皮质对行为的执行控制影响以及促进向自动控制模式的转变至关重要。
