Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour
Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour
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DOI：
10.1007/pl00005494
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发表时间：
1999-10-01
影响因子：
3.4
通讯作者：
Robbins, TW
中科院分区：
文献类型：
--
作者：
Rogers, RD;Blackshaw, AJ;Robbins, TW
原理：5 -羟色胺和多巴胺功能的改变与冲动和冒险行为相关的行为障碍有广泛的联系，然而，很少有研究解决单胺功能改变的具体认知后果，这可能有助于冲动行为的产生。目的与方法：我们比较了血浆色氨酸快速消耗、急性剂量的混合间接儿茶酚胺激动剂哌醋甲酯（40毫克）和急性剂量的α (1)/ α(2)激动剂可口定（1.5 μ g/kg）对视觉辨别学习方面的影响，包括获得改变的刺激-奖励关联（即更新外感刺激的情感效价）或对相关而非无关刺激维度的注意力控制。结果：与接受安慰剂的受试者相比，色氨酸减少的受试者在学习改变的刺激-奖励关联的能力上表现出缺陷，但仍然能够将获得的注意力集从现在无关的刺激维度转移到新的相关维度。相比之下，服用哌醋甲酯的受试者能够有效地学习改变刺激-奖励关联，但表现出更强的转移注意力偏见的能力，同时反应时间也变慢。接受可乐定治疗的受试者没有表现出这些变化。结论：这些结果表明，中枢血清素的减少导致皮层和皮层下区域（如眶额皮质、纹状体和颞叶前部结构）的神经调节改变，这些区域介导联想学习的重要方面，从而使外感受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通过改变背外侧前额叶皮层的调节，扰乱环境中相关和不相关特征之间的注意力分配。这些结果对理解认知功能的差异神经调节的意义进行了讨论。
Rationale: 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. Objectives and methods: 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 mu g/kg), on aspects of visual dis crimination 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. Results: 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. Conclusions: 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.