Didriksen M
Department of Psychopharmacology, St. Hans Hospital, Roskilde, Denmark.
Eur J Pharmacol. 1995 Aug 15;281(3):241-50. doi: 10.1016/0014-2999(95)00242-d.
The acute effects of the dopamine D1 receptor antagonist SCH 23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepi n-7-ol d hemimaleat, the dopamine D2 receptor antagonists raclopride and haloperidol, the compounds with mixed receptor profiles clozapine, risperidone and sertindole, the alpha 1-adrenoceptor antagonist prazosin and scopolamine were investigated in a delay-response task, a test for working memory, for rats. SCH 23390 induced a delay-dependent impairment of the performance. Raclopride, haloperidol, clozapine, and risperidone induced a delay-independent impairment. Sertindole was without effect. The specific (delay-dependent) and unspecific (delay-independent) effects on working memory of the dopamine D1 and D2 receptor antagonists, respectively, were associated with the dominance of dopamine D1 receptors in the prefrontal cortex and of dopamine D2 receptors in the basal structures of the brain. Prazosin did not affect working memory; however, a reduction in intertrial responses was found. Scopolamine induced a delay-independent impairment. It is concluded that the compounds have different activity profiles in this cognitive task. This finding may have important implications for the development of antipsychotics with a lower propensity for cognitive side effects.
在一项延迟反应任务（一种用于测试大鼠工作记忆的试验）中，研究了多巴胺D1受体拮抗剂SCH 23390 [（R）-（+）-8-氯-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇半马来酸盐]、多巴胺D2受体拮抗剂雷氯必利和氟哌啶醇、具有混合受体特征的化合物氯氮平、利培酮和舍吲哚、α1-肾上腺素能受体拮抗剂哌唑嗪以及东莨菪碱的急性效应。SCH 23390诱导了与延迟相关的行为损伤。雷氯必利、氟哌啶醇、氯氮平和利培酮诱导了与延迟无关的损伤。舍吲哚没有效果。多巴胺D1和D2受体拮抗剂分别对工作记忆产生的特异性（与延迟相关）和非特异性（与延迟无关）效应，与多巴胺D1受体在前额叶皮质中的优势以及多巴胺D2受体在脑基底结构中的优势有关。哌唑嗪不影响工作记忆；然而，发现试验间反应减少。东莨菪碱诱导了与延迟无关的损伤。得出的结论是，这些化合物在这项认知任务中具有不同的活性特征。这一发现可能对开发认知副作用倾向较低的抗精神病药物具有重要意义。
