Kienast T, Heinz A
Department of Psychiatry and Psychotherapy, Charité University Medical Center, Schumannstrasse 20-21, 10117 Berlin, Germany.
CNS Neurol Disord Drug Targets. 2006 Feb;5(1):109-31. doi: 10.2174/187152706784111560.
Dysfunction of central dopaminergic neurotransmission has been implicated in a series of neuropsychiatric disorders, including Tourette's syndrome, schizophrenia, and drug and alcohol dependence. The behavioral and psychopathological manifestations of central dopaminergic dysfunction differ depending on the site of their neurobiological correlate. These sites may be found in the dorsal or ventral striatum, but also in cortical regions such as the limbic and prefrontal cortex, among other locations. A low basic dopamine turnover and an increase in the availability of dopamine D2 receptors in the caudate body have been associated with the severity of motor tics in Tourette's syndrome. In the ventral striatum and particularly in the nucleus accumbens, different drugs of abuse stimulate dopamine release and thus reinforce drug consumption. The downregulation of dopamine D2 receptors in this area of the brain has been associated with alcohol craving and an increase in the processing of alcohol-related stimuli in the medial prefrontal cortex. Brain imaging studies in which intrasynaptic dopamine release is manipulated in vivo have shown that increased subcortical dopamine release is associated with the pathogenesis of positive symptoms in schizophrenia. This review discusses a broad range of brain imaging and neuroendocrinological studies on dopaminergic dysfunction in neuropsychiatric disorders, including relevant findings on the basis of primate studies. In addition, the hypothesis is examined that phasic dopamine release is associated with salience attribution to external stimuli, insofar as it mediates reward anticipation in the ventral striatum and limbic cortex, habit formation in the dorsal striatum, and working memory function in the prefrontal cortex.
中枢多巴胺能神经传递功能障碍与一系列神经精神疾病有关，包括图雷特综合征、精神分裂症以及药物和酒精依赖。中枢多巴胺能功能障碍的行为和精神病理表现因其神经生物学关联部位的不同而有所差异。这些部位可能位于背侧或腹侧纹状体，也可能位于边缘和前额叶皮质等皮质区域以及其他部位。基础多巴胺周转率低以及尾状体内多巴胺D2受体可用性增加与图雷特综合征运动抽动的严重程度相关。在腹侧纹状体，尤其是伏隔核，不同的滥用药物会刺激多巴胺释放，从而强化药物消费。大脑这一区域多巴胺D2受体的下调与酒精渴望以及内侧前额叶皮质中与酒精相关刺激的处理增加有关。在体内操纵突触内多巴胺释放的脑成像研究表明，皮质下多巴胺释放增加与精神分裂症阳性症状的发病机制有关。这篇综述讨论了关于神经精神疾病中多巴胺能功能障碍的广泛的脑成像和神经内分泌学研究，包括基于灵长类动物研究的相关发现。此外，还检验了这样一种假说，即阶段性多巴胺释放与对外部刺激的显著性归因有关，因为它介导腹侧纹状体和边缘皮质中的奖励预期、背侧纹状体中的习惯形成以及前额叶皮质中的工作记忆功能。
