Dunn Michael J, Killcross Simon
Department of Health and Social Sciences (Psychology), University of Wales Institute Cardiff, Llandaff Campus, Western Avenue, Cardiff, CF5 2SG, UK.
Psychopharmacology (Berl). 2007 Jun;192(3):347-55. doi: 10.1007/s00213-007-0714-2. Epub 2007 Feb 8.
It has been argued that tasks that necessitate the use of context in the service of goal-directed behaviour are disrupted in both schizophrenic patients and in animal analogues by dopamine (DA) manipulation with the prefrontal cortex being implicated.
To determine the effects on conditional discrimination performance of direct infusion of the DA D(1)/D(2) receptor antagonist alpha-flupenthixol into the medial prefrontal cortex (mPFC) and of its reversal potential on d-amphetamine-induced task disruption.
Conditional discrimination performance in which rats learn to respond on an appropriate lever, conditional upon specific auditory stimuli, was acquired and later tested under the above drug treatment protocol in extinction.
Conditional discrimination performance was unaffected by bilateral intra-mPFC alpha-flupenthixol at doses of 12, 24 or 36 microg/microl. A dose of D-amphetamine (1.5 mg/kg) shown previously to disrupt conditional discrimination performance was attenuated by direct PFC infusion of alpha-flupenthixol at doses of 24 and 36 but not 12 microg/microl per site.
These results show that conditional discrimination performance is at least in part mediated by prefrontal DA as local PFC DA antagonism attenuates task performance disruption by the indirect DA agonist d-amphetamine further implicating the role of dysfunctional forebrain DA in cognitive deficits evident in schizophrenia.
有观点认为，对于精神分裂症患者以及动物模型而言，那些在目标导向行为中需要利用情境的任务，会因多巴胺（DA）的操控而受到干扰，前额叶皮质被认为与此有关。
确定将DA D(1)/D(2)受体拮抗剂阿立哌唑直接注入内侧前额叶皮质（mPFC）对条件辨别性能的影响，以及其对d-苯丙胺引起的任务干扰的逆转潜力。
获取大鼠在特定听觉刺激条件下学会在合适杠杆上做出反应的条件辨别性能，并在上述药物治疗方案下于消退期进行测试。
剂量为12、24或36微克/微升的双侧mPFC内阿立哌唑对条件辨别性能无影响。先前显示会干扰条件辨别性能的d-苯丙胺剂量（1.5毫克/千克），在每部位剂量为24和36微克/微升而非12微克/微升时，通过直接注入前额叶皮质的阿立哌唑得以减弱。
这些结果表明，条件辨别性能至少部分由前额叶多巴胺介导，因为局部前额叶多巴胺拮抗作用减弱了间接多巴胺激动剂d-苯丙胺对任务性能的干扰，这进一步表明功能失调的前脑多巴胺在精神分裂症明显的认知缺陷中所起的作用。
