Rogers R D, Blackshaw A J, Middleton H C, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin J F, Sahakian B J, Robbins T W
Departments of Experimental Psychology and Psychiatry, University of Cambridge, Cambridge, UK.
Psychopharmacology (Berl). 1999 Oct;146(4):482-91. doi: 10.1007/pl00005494.
Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour.
We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the alpha(1)/alpha(2 )agonist, clonidine (1.5 microg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions.
Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes.
These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.
血清素能和多巴胺能功能改变与冲动和冒险相关的行为障碍广泛相关。然而，很少有研究探讨单胺能功能改变可能导致冲动行为产生的具体认知后果。
我们比较了快速血浆色氨酸耗竭、急性剂量的混合间接儿茶酚胺激动剂哌甲酯（40毫克）和急性剂量的α(1)/α(2)激动剂可乐定（1.5微克/千克）对视觉辨别学习方面的影响，这些方面涉及获取改变的刺激-奖励关联（即更新外感受性刺激的情感效价）或控制对相关而非不相关刺激维度的注意力。
相对于接受安慰剂的受试者，色氨酸减少的受试者在学习改变的刺激-奖励关联的能力上存在缺陷，但仍能够将获得的注意力集从现在不相关的刺激维度转移到新的相关维度。相比之下，接受哌甲酯的受试者能够有效地学习改变的刺激-奖励关联，但表现出增强的转移注意力偏差的能力，同时反应时间减慢。接受可乐定的受试者没有表现出这些变化。
这些结果表明，中枢血清素的减少会导致介导联想学习重要方面的皮质和皮质下区域（如眶额皮质、纹状体和颞前结构）的神经调节改变，从而使外感受性刺激获得改变的激励动机价值。另一方面，儿茶酚胺神经递质的促进可能会扰乱对环境相关和不相关特征之间注意力的分配，可能是通过改变背外侧前额叶皮质的调节。讨论了这些结果对理解认知功能差异神经调节的意义。
