Cariprazine, a dopamine D(3)-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse.
Cariprazine, a dopamine D(3)-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse.
复制标题
DOI：
10.1007/s00213-012-2896-5
复制
发表时间：
2013-03
影响因子：
3.4
通讯作者：
Schmauss, Claudia
中科院分区：
文献类型：
--
作者：
Zimnisky, Ross;Chang, Gloria;Gyertyan, Istvan;Kiss, Bela;Adham, Nika;Schmauss, Claudia
精神障碍药物治疗的一个主要挑战是相关认知功能障碍的有效管理。新概念强调了作用于多巴胺D2样受体的部分激动剂在改善这些认知缺陷中的潜在益处，并且临床前研究表明D3受体偏好化合物可以发挥促认知作用。本研究的目的是使用急性苯环利定（PCP）治疗来模拟小鼠精神分裂症的认知缺陷，并检测新型多巴胺D3受体偏好药物卡利拉嗪在改善PCP触发的认知缺陷严重程度方面的疗效。一组野生型或D3受体敲除小鼠用盐水或苯环利定（PCP，1 mg/kg）进行急性治疗。在PCP给药前，单独一组小鼠接受卡利拉嗪给药。然后，两组都进行了三项认知任务的测试：社会互动/识别和识别记忆，空间工作记忆和注意力转移。PCP有效地破坏了社会认知和社会认知记忆，空间工作记忆和额外维度的注意力转移。卡利拉嗪预处理显著减弱了PCP给药野生型小鼠中这些认知缺陷的出现，但在PCP给药D3受体敲除小鼠中未出现。在PCP诱导的认知损害动物模型中，卡利拉嗪预处理显著减少了PCP触发的认知缺陷，对敲除小鼠的研究表明多巴胺D3受体促成了该效应。
A major challenge in the pharmacological treatment of psychotic disorders is the effective management of the associated cognitive dysfunctions. Novel concepts emphasize a potential benefit of partial agonists acting upon dopamine D2-like receptors in ameliorating these cognitive deficits, and pre-clinical studies suggest that D3-receptor-preferring compounds can exert pro-cognitive effects. The objective of the study was to use acute phencyclidine (PCP) treatment to model the cognitive deficits of schizophrenia in mice, and to test the efficacy of the novel, dopamine D3-receptor-preferring drug cariprazine in ameliorating the severity of PCP-triggered cognitive deficits. One group of wild-type or D3-receptor knockout mice was acutely treated with either saline or phencyclidine (PCP, 1 mg/kg). A separate group of mice was treated with cariprazine prior to PCP administration. Both groups were then tested in three cognitive tasks: social interaction/recognition and recognition memory, spatial working memory, and attention-set-shifting. PCP effectively disrupted social recognition and social recognition memory, spatial working memory, and extradimensional attention set-shifting. Cariprazine pretreatment significantly attenuated the emergence of these cognitive deficits in PCP-treated wild-type mice, but not in PCP-treated D3-receptor knockout mice. In an animal model of PCP-induced cognitive impairment, cariprazine pretreatment significantly diminished PCP-triggered cognitive deficits, and studies on knockout mice show that dopamine D3 receptors contribute to this effect.
登录
查看更多内容
影响因子：
3.3
作者：
Desteno, D. A.;Schmauss, C.
通讯作者：
Schmauss, C.
DOI：
10.1176/appi.ajp.2011.10081209
发表时间：
2011-08
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Carrión RE;Goldberg TE;McLaughlin D;Auther AM;Correll CU;Cornblatt BA
通讯作者：
Cornblatt BA
影响因子：
3.4
作者：
Jentsch, JD;Anzivino, LA
通讯作者：
Anzivino, LA
影响因子：
3.7
作者：
Glickstein, SB;DeSteno, DA;Schmauss, C
通讯作者：
Schmauss, C
影响因子：
4.5
作者：
Nuechterlein, KH;Barch, DM;Heaton, RK
通讯作者：
Heaton, RK