School of Psychology, University of Leicester, Leicester, UK.
J Psychopharmacol. 2011 Jun;25(6):792-800. doi: 10.1177/0269881110387840. Epub 2010 Nov 18.
This study investigated the effects of the dopamine D(4) receptor agonist, PD168077, on recognition memory using a novel object recognition task, which detects disruption and improvement of recognition memory in rats by measuring their ability to discriminate between familiar and novel objects. When acquisition and test were 6 h apart (experiment 1), control rats failed to discriminate between familiar and novel objects at test. Rats given low doses of PD168077 (0.3; 1.0 mg/kg) also failed to discriminate between the objects, while rats given higher doses (3.0; 10.0 mg/kg) explored the novel object more than the familiar object, indicating retained memory of the familiar object. Thus, at higher doses, PD168077 improved recognition memory in rats. Experiment 2 tested whether PD168077 would attenuate deficits in novel object recognition induced by sub-chronic phencyclidine. Testing was 1 min after acquisition, such that vehicle pre-treated rats differentiated between the novel and familiar objects: however, sub-chronic phencyclidine-treated rats failed to discriminate between the two, indicating disruption of recognition memory. PD168077 (10 mg/kg) restored the ability of phencyclidine-treated rats to differentiate between the novel and familiar objects, indicating improved recognition memory. The results suggest that D(4) receptor activation can improve cognitive dysfunction in an animal model relevant to schizophrenia.
这项研究使用新物体识别任务考察了多巴胺 D(4)受体激动剂 PD168077 对识别记忆的影响，该任务通过测量大鼠区分熟悉和新物体的能力来检测识别记忆的破坏和改善。当获得和测试相隔 6 小时（实验 1）时，对照组大鼠在测试中无法区分熟悉和新物体。给予低剂量 PD168077（0.3；1.0mg/kg）的大鼠也无法区分物体，而给予高剂量（3.0；10.0mg/kg）的大鼠对新物体的探索多于熟悉物体，表明对熟悉物体的记忆保留。因此，在较高剂量下，PD168077 改善了大鼠的识别记忆。实验 2 测试了 PD168077 是否会减弱亚慢性苯环己哌啶引起的新物体识别缺陷。测试是在获得后 1 分钟进行的，因此，给予载体预处理的大鼠能够区分新物体和熟悉物体：然而，亚慢性苯环己哌啶处理的大鼠无法区分两者，表明识别记忆受损。PD168077（10mg/kg）恢复了苯环己哌啶处理的大鼠区分新物体和熟悉物体的能力，表明识别记忆得到改善。结果表明，D(4)受体激活可以改善与精神分裂症相关的动物模型中的认知功能障碍。
