Tenn Catherine C, Fletcher Paul J, Kapur Shitij
Schizophrenia/PET Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto Canada.
Biol Psychiatry. 2005 Mar 15;57(6):586-93. doi: 10.1016/j.biopsych.2004.12.013.
There is growing interest in detecting and treating schizophrenia during the "prodrome," before the symptoms are fully manifested. The objective of this study was to develop a putative model of the prodrome and study the effects of medications on it.
Rats were treated with different regimens of amphetamine to produce full sensitization (full syndrome) and partial sensitization (to model the prodromal state) and were then treated with typical and atypical antipsychotics and a D1 antagonist to mimic early intervention. After several weeks of withdrawal, locomotor activity in response to amphetamine and behavioral deficits (prepulse inhibition [PPI] and latent inhibition [LI]) were examined.
Animals that received the full sensitization showed significant increase in locomotor activity and a disruption in both PPI and LI. Animals treated with a partial regimen showed only a muted phenotype. The animals that received "early intervention" did not show progression from the prodromal to the full-blown phenotype.
The partial regimen of amphetamine injections provided a modified phenotype that could be regarded as a representative of the "prodromal" state. Early intervention, instituted once the prodromal state was already developed, prevented further progression into the full phenotype analogous to schizophrenia.
在精神分裂症症状完全显现之前的“前驱期”进行检测和治疗，受到越来越多的关注。本研究的目的是建立一个前驱期的假定模型，并研究药物对其的影响。
用不同剂量的苯丙胺处理大鼠，以产生完全敏感化（完全综合征）和部分敏感化（模拟前驱状态），然后用典型和非典型抗精神病药物以及一种D1拮抗剂进行处理，以模拟早期干预。在停药几周后，检测大鼠对苯丙胺的运动活性以及行为缺陷（前脉冲抑制[PPI]和潜伏抑制[LI]）。
接受完全敏感化处理的动物运动活性显著增加，PPI和LI均受到破坏。接受部分处理方案的动物仅表现出轻微的表型。接受“早期干预”的动物没有从前驱期发展为全面发作的表型。
苯丙胺注射的部分处理方案提供了一种改变的表型，可被视为“前驱期”状态的代表。一旦前驱期已经形成，进行早期干预可防止进一步发展为类似于精神分裂症的全面表型。
