Garavan Hugh, Kaufman Jacqueline N, Hester Robert
Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin 2, Ireland.
Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3267-76. doi: 10.1098/rstb.2008.0106.
Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous cocaine administration improved task performance in 13 cocaine users. This improvement was accompanied by increased activation in right dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function. Similarly, for both inhibitory control and action monitoring processes, cocaine normalized activation levels in lateral and medial prefrontal regions previously reported to be hypoactive in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction may reflect a chronic dysregulation of those brain regions and the cognitive processes they subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive control.
对药物冲动和觅药行为施加控制的能力受损是成瘾的一个特征。一种特定的认知控制功能，即冲动控制，已被证明是出现物质问题的一个风险因素，并且在动物模型中与药物使用增加和复吸有关。我们提供了可卡因对冲动控制背后的神经生物学产生直接影响的证据。在一项运动反应抑制的实验室测试中，静脉注射可卡因提高了13名可卡因使用者的任务表现。这种改善伴随着右侧背外侧和额下回皮质激活增加，这些区域被认为对这种认知功能至关重要。同样，对于抑制控制和动作监测过程，可卡因使外侧和内侧前额叶区域的激活水平正常化，先前报道这些区域在使用者中相对于未使用药物的对照表现为活动不足。神经认知功能障碍的急性改善可能反映了这些脑区及其所支持的认知过程的慢性失调。此外，可卡因对中线功能的影响表明，在可卡因的急性强化作用与其对认知控制的作用之间存在多巴胺能介导的交叉点。
