Division of Psychiatry and Behavioural Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Behav Brain Res. 2013 Jun 15;247:158-64. doi: 10.1016/j.bbr.2013.03.027. Epub 2013 Mar 26.
Blonanserin is an atypical antipsychotic drug (APD) which, compared to other atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist. Comparing blonanserin with more broadly acting atypical APDs could be useful to test the contributions of actions at other monoamine receptors, e.g. 5-HT1A receptors, to the reversal of PCP-induced novel object recognition (NOR) deficit. In this study, we tested the effect of blonanserin alone, and in combination with 5-HT1A agents, on NOR deficit induced by subchronic treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP; 2 mg/kg), b.i.d., for 7 days. Blonanserin, 1mg/kg, but not 0.3mg/kg, improved the PCP-induced NOR deficit. However, at 1mg/kg, object exploration was diminished. Co-administration of sub-effective doses of blonanserin (0.3 mg/kg) and the 5-HT1A partial agonist, tandospirone (0.2 mg/kg), significantly reversed the NOR deficit without diminishing activity during the acquisition or retention periods. The combination of WAY100635 (0.6 mg/kg), a 5-HT1A antagonist, and blonanserin (1 mg/kg), also diminished object exploration which prevented assessment of the effect of this combination on NOR. WAY100635 (0.6 mg/kg) blocked the ameliorating effect of risperidone (0.1 mg/kg), another atypical APD with low affinity for 5-HT1A receptors, but did not impair exploration. These results suggest that blonansein and risperidone, atypical APDs which lack a direct action on 5-HT1A receptors require 5-HT1A receptor stimulation to reverse the subchronic PCP-induced NOR deficit and provide a support for clinical trial of blonanserin in combination with tandospirone to ameliorate cognitive impairment in schizophrenia and to have fewer side effects.
布南色林是一种非典型抗精神病药物（APD），与其他非典型 APD 相比，它对 5-羟色胺（5-HT）2A 和多巴胺 D2 具有相对选择性。将布南色林与作用更广泛的非典型 APD 进行比较，可以有助于测试其他单胺受体（如 5-HT1A 受体）的作用对逆转 PC 诱导的新物体识别（NOR）缺陷的贡献。在这项研究中，我们测试了布南色林单独使用以及与 5-HT1A 药物联合使用对亚慢性治疗 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环己哌啶（PCP；2mg/kg，每日两次）引起的 NOR 缺陷的影响，共 7 天。布南色林（1mg/kg），而不是 0.3mg/kg，改善了 PCP 诱导的 NOR 缺陷。然而，在 1mg/kg 时，物体探索减少了。亚有效剂量的布南色林（0.3mg/kg）和 5-HT1A 部分激动剂坦度螺酮（0.2mg/kg）联合给药，显著逆转了 NOR 缺陷，而在获得期和保留期期间没有减少活动。5-HT1A 拮抗剂 WAY100635（0.6mg/kg）和布南色林（1mg/kg）的组合也减少了物体探索，这阻止了评估该组合对 NOR 的影响。WAY100635（0.6mg/kg）阻断了利培酮（0.1mg/kg）的改善作用，利培酮是另一种对 5-HT1A 受体亲和力低的非典型 APD，但不损害探索。这些结果表明，布南色林和利培酮这两种缺乏对 5-HT1A 受体直接作用的非典型 APD，需要 5-HT1A 受体刺激来逆转亚慢性 PCP 诱导的 NOR 缺陷，并为临床试验提供支持，即联合使用布南色林和坦度螺酮来改善精神分裂症的认知障碍，并减少副作用。
