Kozak Rouba, Martinez Vicente, Young Damon, Brown Holden, Bruno John P, Sarter Martin
Department of Psychology, University of Michigan, Ann Arbor, MI 48109-1043, USA.
Neuropsychopharmacology. 2007 Oct;32(10):2074-86. doi: 10.1038/sj.npp.1301352. Epub 2007 Feb 14.
Impairments in attentional functions and capacities represent core aspects of the cognitive symptoms of schizophrenia. Attentional performance has been demonstrated to depend on the integrity and activity of cortical cholinergic inputs. The neurobiological, behavioral, and cognitive effects of repeated exposure to psychostimulants model important aspects of schizophrenia. In the present experiment, prefrontal acetylcholine (ACh) release was measured in attentional task-performing and non-performing rats pretreated with an escalating dosing regimen of amphetamine (AMPH) and following challenges with AMPH. In non-performing rats, pretreatment with AMPH did not affect the increases in ACh release produced by AMPH-challenges. In contrast, attentional task performance-associated increases in ACh release were attenuated in AMPH-pretreated and AMPH-challenged rats. This effect of repeated AMPH exposure on ACh release was already present before task-onset, suggesting that the loss of cognitive control that characterized these animals' performance was a result of cholinergic dysregulation. The findings indicate that the demonstration of repeated AMPH-induced dysregulation of the prefrontal cholinergic input system depends on interactions between the effects of repeated AMPH exposure and cognitive performance-associated recruitment of this neuronal system. Repeated AMPH-induced disruption of prefrontal cholinergic activity and attentional performance represents a useful model to investigate the cholinergic mechanisms contributing to the cognitive impairments of schizophrenia.
注意力功能和能力受损是精神分裂症认知症状的核心方面。注意力表现已被证明取决于皮质胆碱能输入的完整性和活性。反复接触精神兴奋剂的神经生物学、行为学和认知效应模拟了精神分裂症的重要方面。在本实验中，测量了用递增剂量方案预处理安非他明（AMPH）并在接受AMPH激发后执行和未执行注意力任务的大鼠前额叶乙酰胆碱（ACh）释放情况。在未执行任务的大鼠中，AMPH预处理不影响AMPH激发引起的ACh释放增加。相反，在接受AMPH预处理和激发的大鼠中，与注意力任务表现相关的ACh释放增加减弱。反复接触AMPH对ACh释放的这种影响在任务开始前就已存在，这表明这些动物表现中所特有的认知控制丧失是胆碱能调节异常的结果。这些发现表明，反复AMPH诱导的前额叶胆碱能输入系统调节异常的表现取决于反复AMPH暴露的影响与该神经元系统与认知表现相关的募集之间的相互作用。反复AMPH诱导的前额叶胆碱能活性破坏和注意力表现是研究导致精神分裂症认知障碍的胆碱能机制的有用模型。
