Glenthøj B Y
Department of Psychiatry, Rigshospitalet, Copenhagen.
Dan Med Bull. 1995 Feb;42(1):1-21.
The kindling phenomenon is a good example of the effect of multiplicity on response increment processes in the nervous system. The electrical potentiation resembles pharmacological sensitization. An intermittent regimen is essential for a progressive augmentation of the behavioural response in both conditions. Nigro-striatal dopaminergic sensitization by on and off anti-dopaminergic drugs has been suggested as a model for development of tardive dyskinesia (TD) and sensitization of the meso-limbic dopaminergic system either by repeated stimulation with agonists or by environmental stressors has been proposed to model psychotic development in schizophrenia. The present thesis addresses the implications of intermittent influences on the brain dopaminergic systems for the development of pathological behaviours. For this purpose new rat models have been developed both for studying the effects of the treatment schedule of neuroleptics on the development of oral hyperactivity and for studying the effects of intermittent electrical stimulations of the ventral tegmental area (VTA) housing the meso-limbic dopamine (DA) cells. A long-lasting/permanent kindling-like sensitization to the dyskinetic inducing side-effects of classical neuroleptic drugs following intermittent opposed to continuous treatment has been demonstrated. This sensitization is proposed to represent an animal model for TD. The significance of receptor profiles, the effects of pharmacological interventions and the possible relation to the GABAergic and cholinergic systems are discussed. Intermittent electrical activation of the cells in the VTA resulted in a syndrome characterized by a hypersensitive response to electrical or pharmacological dopaminergic provocation combined with abnormal social interactions. This new animal model may have implications for the understanding of the pathogenesis of schizophrenia. Hypotheses are proposed for the meaning of dopaminergic sensitization both in the development of persisting dyskinetic side-effects related to neuroleptic treatment and in the development of schizophrenia.
点燃现象是多重性对神经系统反应增强过程影响的一个很好的例子。电增强类似于药理学致敏。在这两种情况下，间歇性给药方案对于行为反应的逐步增强至关重要。关与开抗多巴胺能药物引起的黑质-纹状体多巴胺能致敏已被认为是迟发性运动障碍（TD）发展的模型，并且中脑-边缘多巴胺能系统通过激动剂反复刺激或环境应激源致敏已被提出作为精神分裂症精神病发展的模型。本论文探讨间歇性影响对脑多巴胺能系统的影响对病理行为发展的意义。为此，已开发出新的大鼠模型，用于研究抗精神病药物治疗方案对口腔多动发展的影响，以及用于研究对中脑-边缘多巴胺（DA）细胞所在的腹侧被盖区（VTA）进行间歇性电刺激的影响。已证明，与持续治疗相比，间歇性治疗后对经典抗精神病药物致运动障碍副作用的长期/永久性点燃样致敏。这种致敏被认为代表了TD的动物模型。讨论了受体谱的意义、药理学干预的效果以及与GABA能和胆碱能系统的可能关系。VTA中细胞的间歇性电激活导致一种综合征，其特征是对电或药理学多巴胺能激发的超敏反应以及异常的社交互动。这种新的动物模型可能对理解精神分裂症的发病机制有意义。针对多巴胺能致敏在与抗精神病药物治疗相关的持续性运动障碍副作用发展以及精神分裂症发展中的意义提出了假设。
