Sarter M, Bruno J P, Berntson G G
Department of Psychology, The Ohio State University, Columbus 43210, USA.
Psychopharmacology (Berl). 2001 Jun;156(1):1-13. doi: 10.1007/s002130100756.
The neurochemical, behavioral, and cognitive effects of the benzodiazepine receptor partial inverse agonist beta-carboline FG 7142 (FG), a drug traditionally described as exhibiting 'anxiogenic' effects, are proposed to model core components of present theories of the neuronal mechanisms of schizophrenia. FG activates the mesolimbic dopaminergic system and, via increases in dopaminergic activity in the nucleus accumbens, disinhibits corticopetal cholinergic projections. The latter effect of FG is hypothesized to mediate the hyperattentional impairments that contribute to the development of psychotic cognition. Furthermore, the FG-induced abnormal overprocessing of conditioned stimuli and contexts provides an explanation of the 'anxiogenic' effects of FG. The FG-induced increases in the activity of cortical cholinergic inputs and the FG-induced cognitive impairments in rats and monkeys were demonstrated to be attenuated by the administration of typical and atypical antipsychotic drugs. Compared to the classic psychotogenic drugs amphetamine and phencyclidine, the effects of FG serve as an alternative psychotogenic manipulation in research focusing on the cortical and cognitive aspects of current theories of schizophrenia.
苯二氮䓬受体部分反向激动剂β-咔啉FG 7142（FG），一种传统上被描述为具有“致焦虑”作用的药物，其神经化学、行为和认知效应被认为可模拟当前精神分裂症神经元机制理论的核心成分。FG激活中脑边缘多巴胺能系统，并通过增加伏隔核中的多巴胺能活性，解除对向皮质投射的胆碱能神经纤维的抑制。FG的后一种作用被假设为介导导致精神病性认知发展的过度注意力损伤。此外，FG诱导的条件刺激和情境的异常过度加工为FG的“致焦虑”作用提供了解释。已证明，给予典型和非典型抗精神病药物可减轻FG诱导的大鼠和猴子皮质胆碱能输入活性增加以及FG诱导的认知损伤。与经典的致幻药物苯丙胺和苯环利定相比，在关注当前精神分裂症理论的皮质和认知方面的研究中，FG的作用可作为一种替代性的致幻操作。
