Broersen L.M., Heinsbroek R.P.W., de Bruin J.P.C., Laan J.-B., Joosten R.N.J.M.A., Olivier B.
Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands.
Behav Pharmacol. 1995 Jun;6(4):395-404.
Several lines of research have implicated the prefrontal cortex (PFC) and its dopaminergic (DA) innervation in an animal's response to stress and anxiety. To extend these findings we evaluated the effects of bilateral infusions of DA drugs into the medial PFC of rats, in a modified conflict test, consisting of Reward, Conflict and Time-out components. In experiment 1, the effects of infusions of the DA receptor agonist apomorphine (APO) were compared to the effects of systemic injections of the same drug. APO infusions induced a dose-dependent decrease of responding in the Conflict component, indicative of an anxiogenic-like effect. However, response rates in the Reward component were simultaneously decreased, casting some doubt on the specificity of the effect. In comparison, i.p injections of APO in a second group of animals did not affect responding in the Conflict component, but dose-dependently decreased response rates during Time-out and Reward components. In experiment 2, we evaluated the effects of infusions of APO and the DA receptor antagonist cis-flupenthixol (FLU) into the medial PFC in the conflict test, and in one of its variants, the extinction of conflict test. Although both APO and FLU decreased response rates during Reward components, responding in the Conflict components of both tests was differentially affected. APO infusions decreased Conflict responses, the effect being more pronounced in the extinction of conflict test. In contrast, infusions of FLU increased responding in the Conflict components. The respective pro- and anti-conflict effects of APO and FLU infusions are in favour of a direct involvement of prefrontal DA in anxiety-related behavioural responses.
多项研究表明，前额叶皮层（PFC）及其多巴胺能（DA）神经支配与动物对应激和焦虑的反应有关。为了扩展这些发现，我们在一项改良的冲突测试中评估了向大鼠内侧前额叶皮层双侧注射DA药物的效果，该测试包括奖励、冲突和暂停三个部分。在实验1中，将DA受体激动剂阿扑吗啡（APO）注射的效果与全身注射相同药物的效果进行了比较。APO注射导致冲突部分的反应呈剂量依赖性降低，表明具有类似焦虑的作用。然而，奖励部分的反应率同时降低，这对该效果的特异性产生了一些疑问。相比之下，在第二组动物中腹腔注射APO对冲突部分的反应没有影响，但在暂停和奖励部分剂量依赖性地降低了反应率。在实验2中，我们在冲突测试及其变体之一——冲突测试消退中，评估了向内侧前额叶皮层注射APO和DA受体拮抗剂顺式氟奋乃静（FLU）的效果。尽管APO和FLU都降低了奖励部分的反应率，但两种测试的冲突部分的反应受到了不同的影响。APO注射降低了冲突反应，在冲突测试消退中这种效果更明显。相比之下，FLU注射增加了冲突部分的反应。APO和FLU注射各自的促冲突和抗冲突作用支持前额叶DA直接参与与焦虑相关的行为反应。
