Dopaminergic modulation of the orbitofrontal cortex affects attention, motivation and impulsive responding in rats performing the five-choice serial reaction time task

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• 作者：Catharine A. Winstanley ; Fiona D. Zeeb ; Am ; a Bedard ; Kent Fu ; Barbara Lai ; Christina Steele ; Adeline C. Wong
• 关键词：Impulsivity ; Dopamine ; Orbitofrontal cortex ; Baseline-dependency ; D₁ receptor ; D₂ receptor
• 刊名：Behavioural Brain Research
• 出版年：2010
• 出版时间：11 July 2010
• 年：2010
• 卷：210
• 期：2
• 页码：263-272
• 全文大小：762 K

文摘

Understanding the neurobiological factors underlying individual differences in impulsivity may provide valuable insight into vulnerability to impulse control disorders. Recent data implicate both the orbitofrontal cortex (OFC) and the dopaminergic system in psychiatric disorders associated with high levels of impulsivity, including substance abuse, mania and obsessive–compulsive disorder. However, the consequences of modulating dopaminergic activity within the OFC on impulsive behaviour are largely unknown. The effects of direct intra-OFC infusions of agonists and antagonists at the dopamine D₁ and D₂ receptors were therefore assessed in rats performing the five-choice serial reaction time test (5CSRT) of attention and motor impulsivity. Intra-OFC administration of SCH23390, a D₁ receptor antagonist, decreased impulsive responding in highly impulsive (HI) rats, but did not affect behaviour in less impulsive (LI) animals. Furthermore, the D₂ agonist quinpirole caused significant deficits in task performance, impairing accuracy, increasing omissions and decreasing the number of trials completed, which resembled the effects of systemic administration. In contrast, the D₁ agonist SKF 81297 had little effect on behaviour. Neither agonist increased impulsivity. These data provide partial support for the suggestion that high levels of impulsivity are associated with increased dopamine levels within the OFC, but further indicate that simulating dopamine's actions selectively at the D₁ or D₂ receptor cannot reproduce a highly impulsive phenotype. Dopaminergic activity within the OFC may therefore modulate impulsivity indirectly, perhaps in conjunction with other neurotransmitter systems. Furthermore, D₂-mediated neurotransmission within the OFC could make a more fundamental contribution to cognitive behaviour.