O'Tuathaigh C M P, Moran P M
Department of Psychology, University of Leicester, University Road, Leicester LE1 7RH, UK.
Psychopharmacology (Berl). 2002 Jul;162(3):225-31. doi: 10.1007/s00213-002-1107-1. Epub 2002 May 14.
A number of lines of evidence suggest that dopamine might play a role in stimulus selection, the process whereby specific cues are selected to guide action.
In order further to define the potential role for dopamine in stimulus selection, the present series of studies examined whether dopaminergic drugs modulate overshadowing, a paradigm that involves stimulus selection in rats. Overshadowing is where preferential learning occurs to one (usually the more salient) element of a stimulus compound.
Overshadowing was measured in rats using a thirst motivated conditioned emotional response paradigm (CER). Two simultaneously presented stimuli (light and tone) were paired with an aversive unconditioned stimulus (mild footshock); overshadowing is observed when learning to the less salient stimulus is weaker than learning to the same stimulus when it is conditioned alone.
d-Amphetamine sulphate (1 mg/kg, IP) was found selectively to disrupt overshadowing, without affecting the CER in control animals. The dopamine (DA) D(2) receptor antagonists, haloperidol (0.2 mg/kg, IP) or raclopride (0.5 mg/kg, IP), failed to reverse amphetamine-induced disruption of overshadowing. In contrast, the selective DA D(1) antagonist SCH 23390 (0.05 mg/kg, IP) reversed amphetamine-induced disruption of overshadowing. The partial DA D(1) agonist SKF 38393 (5 mg/kg, IP) was found to abolish overshadowing when given alone.
These data indicate a modulatory role for the DA D(1) receptor in the expression of stimulus selection and suggest that the DA D(1) receptor might play a role in salience allocation aspects of learning.
多项证据表明,多巴胺可能在刺激选择过程中发挥作用,刺激选择是指选择特定线索以指导行动的过程。
为了进一步明确多巴胺在刺激选择中的潜在作用,本系列研究考察了多巴胺能药物是否会调节遮蔽效应,遮蔽效应是一种涉及大鼠刺激选择的范式。遮蔽效应是指对刺激复合物中某一(通常是更显著的)元素出现优先学习的现象。
采用口渴动机条件性情绪反应范式(CER)在大鼠中测量遮蔽效应。将两个同时呈现的刺激(光和声音)与厌恶非条件刺激(轻度足部电击)配对;当对不太显著的刺激的学习比单独对相同刺激进行条件反射时的学习更弱时,就会观察到遮蔽效应。
发现硫酸右苯丙胺(1毫克/千克,腹腔注射)能选择性地破坏遮蔽效应,而不影响对照动物的CER。多巴胺(DA)D(2)受体拮抗剂氟哌啶醇(0.2毫克/千克,腹腔注射)或雷氯必利(0.5毫克/千克,腹腔注射)未能逆转苯丙胺引起的遮蔽效应破坏。相比之下,选择性DA D(1)拮抗剂SCH 23390(0.05毫克/千克,腹腔注射)逆转了苯丙胺引起的遮蔽效应破坏。发现部分DA D(1)激动剂SKF 38393(5毫克/千克,腹腔注射)单独给药时可消除遮蔽效应。
这些数据表明DA D(1)受体在刺激选择表达中具有调节作用,并表明DA D(1)受体可能在学习的显著性分配方面发挥作用。