Dopamine D1 and D3 Receptors Modulate Heroin-Induced Cognitive Impairment through Opponent Actions in Mice.
Dopamine D1 and D3 Receptors Modulate Heroin-Induced Cognitive Impairment through Opponent Actions in Mice.
复制标题
多巴胺 D-1 和 D-3 受体通过小鼠的对抗行为调节海洛因引起的认知障碍
DOI：
10.1093/ijnp/pyw099
复制
发表时间：
2017-03-01
期刊：
影响因子：
--
通讯作者：
Yin F
中科院分区：
文献类型：
--
作者：
Zhu Y;Wang Y;Lai J;Wei S;Zhang H;Yan P;Li Y;Qiao X;Yin F
长期滥用海洛因会导致持久而复杂的认知障碍。多巴胺受体与冲动的药物驱动行为以及与较高复发率相关的注意力、处理速度和心理灵活性的改变密切相关。然而，不同的多巴胺受体的作用以及它们可能参与海洛因诱导的认知障碍仍不清楚。采用5选一系列反应时任务研究海洛因所致小鼠认知功能障碍的特点。测定前额叶皮质、伏隔核和尾壳核中多巴胺D_1和D_2样受体的表达水平。在D_1和D_3受体突变小鼠上，通过激动剂/拮抗剂处理，观察多巴胺受体对海洛因诱发冲动的影响。全身注射海洛因影响了5项连续反应时间任务中的几个变量，最显著的是早产反应，这是一种衡量运动冲动的指标。这些行为障碍与观察到的3个脑区的D1受体增加和D3受体mRNA和蛋白水平降低有关。海洛因引起的早熟反应的增加被一种D1激动剂模拟，并被一种D1拮抗剂或D1受体基因的遗传消融所阻止。相比之下，D3激动剂降低了基础和海洛因诱发的早熟反应，而基因切割D3受体基因会导致基础和海洛因诱发的早熟反应增加。在5个选择的系列反应时间任务中，海洛因诱发的冲动行为受到D1和D3受体激活的相反调节。大脑皮层-中脑边缘区的D1受体在调节这种行为中起着不可或缺的作用。
Chronic abuse of heroin leads to long-lasting and complicated cognitive impairment. Dopamine receptors are critically involved in the impulsive drug-driven behavior and the altered attention, processing speed, and mental flexibility that are associated with higher relapse rates. However, the effects of the different dopamine receptors and their possible involvement in heroin-induced cognitive impairment remain unclear. The 5-choice serial reaction time task was used to investigate the profiles of heroin-induced cognitive impairment in mice. The expression levels of dopamine D1- and D2-like receptors in the prefrontal cortex, nucleus accumbens, and caudate-putamen were determined. The effects of dopamine receptors on heroin-induced impulsivity in the 5-choice serial reaction time task were examined by agonist/antagonist treatment on D1 or D3 receptor mutant mice. Systemic heroin administration influences several variables in the 5-choice serial reaction time task, most notably premature responses, a measure of motor impulsivity. These behavioral impairments are associated with increased D1 receptor and decreased D3 receptor mRNA and protein levels in 3 observed brain areas. The heroin-evoked increase in premature responses is mimicked by a D1 agonist and prevented by a D1 antagonist or genetic ablation of the D1 receptor gene. In contrast, a D3 agonist decreases both basal and heroin-evoked premature responses, while genetic ablation of the D3 receptor gene results in increased basal and heroin-evoked premature responses. Heroin-induced impulsive behavior in the 5-choice serial reaction time task is oppositely modulated by D1 and D3 receptor activation. The D1 receptors in the cortical-mesolimbic region play an indispensable role in modulating such behaviors.