Abstract：
BACKGROUND: The 5-HT2A receptor is the major target of classic hallucinogens. Both DOI (2,5-dimethoxy-4-iodoamphetamine) and lisuride act at 5-HT2A receptors, and lisuride shares comparable affinity with DOI and acts as a partial agonist at 5-HT2A receptors. However, not like DOI, lisuride lacks hallucinogenic properties. Impulsive decision-making refers to the preference for an immediate small reinforcer (SR) over a delayed large reinforcer (LR).
OBJECTIVE: The current study aims to compare the effects of DOI and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs.
METHODS: Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percentage of choice for the LR in delay discounting task (DDT). Delay to the LR changed in an ascending order (0, 4, 8, 16, and 32 s) across one session.
RESULTS: DOI (0.5 and 1.0 mg/kg) increased impulsive decision-making, and the effects of DOI (1.0 mg/kg) were blocked by the 5-HT2A receptor antagonist ketanserin (1.0 mg/kg) rather than the 5-HT2C receptor antagonist SB-242084 (1.0 mg/kg). Contrarily, lisuride (0.1, 0.3, and 0.5 mg/kg) decreased impulsive decision-making. The effects of lisuride (0.3 mg/kg) were not antagonized by ketanserin (1.0 mg/kg), selective 5-HT1A antagonist WAY-100635 (1.0 mg/kg), or selective dopamine D4 receptor antagonist L-745870 (1.0 mg/kg) but were attenuated by the selective dopamine D2/D3 receptor antagonist tiapride (40 mg/kg).
CONCLUSIONS: DOI and lisuride have contrasting effects on impulsive decision-making via distinct receptors. DOI-induced increase of impulsivity is mediated by the 5-HT2A receptor, while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.
OBJECTIVE: The current study aims to compare the effects of DOI and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs.
METHODS: Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percentage of choice for the LR in delay discounting task (DDT). Delay to the LR changed in an ascending order (0, 4, 8, 16, and 32 s) across one session.
RESULTS: DOI (0.5 and 1.0 mg/kg) increased impulsive decision-making, and the effects of DOI (1.0 mg/kg) were blocked by the 5-HT2A receptor antagonist ketanserin (1.0 mg/kg) rather than the 5-HT2C receptor antagonist SB-242084 (1.0 mg/kg). Contrarily, lisuride (0.1, 0.3, and 0.5 mg/kg) decreased impulsive decision-making. The effects of lisuride (0.3 mg/kg) were not antagonized by ketanserin (1.0 mg/kg), selective 5-HT1A antagonist WAY-100635 (1.0 mg/kg), or selective dopamine D4 receptor antagonist L-745870 (1.0 mg/kg) but were attenuated by the selective dopamine D2/D3 receptor antagonist tiapride (40 mg/kg).
CONCLUSIONS: DOI and lisuride have contrasting effects on impulsive decision-making via distinct receptors. DOI-induced increase of impulsivity is mediated by the 5-HT2A receptor, while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.
摘要：
背景：5-HT2A受体是经典致幻剂的主要靶标。DOI（2,5-二甲氧基-4-碘苯丙胺）和石脲内酯均作用于5-HT2A受体，和利苏利德与DOI具有相当的亲和力，并充当5-HT2A受体的部分激动剂。然而,不像DOI,利苏利特缺乏致幻特性。冲动性决策是指对直接的小型增强剂（SR）比对延迟的大型增强剂（LR）的偏好。
目的：本研究旨在比较DOI和利苏利特对冲动性决策的影响，并进一步研究负责这两种药物作用的可能受体机制。
方法：通过延迟贴现任务（DDT）中LR的选择百分比来评估雄性Sprague-Dawley大鼠的冲动性决策。LR的延迟在一个会话中以升序(0、4、8、16和32s)改变。
结果：DOI（0.5和1.0mg/kg）增加了冲动性决策，DOI（1.0mg/kg）的作用被5-HT2A受体拮抗剂ketanserin（1.0mg/kg）而不是5-HT2C受体拮抗剂SB-242084（1.0mg/kg）阻断。相反，利苏利特（0.1、0.3和0.5mg/kg）减少了冲动性决策。利苏利特（0.3mg/kg）的作用未被酮色林（1.0mg/kg）拮抗，选择性5-HT1A拮抗剂WAY-100635（1.0mg/kg），或选择性多巴胺D4受体拮抗剂L-745870（1.0mg/kg），但被选择性多巴胺D2/D3受体拮抗剂tiapride（40mg/kg）减毒。
结论：DOI和利苏利特通过不同的受体对冲动决策有对比作用。DOI诱导的冲动增加是由5-HT2A受体介导的，而利脲诱导的冲动抑制受多巴胺D2/D3受体调节。
目的：本研究旨在比较DOI和利苏利特对冲动性决策的影响，并进一步研究负责这两种药物作用的可能受体机制。
方法：通过延迟贴现任务（DDT）中LR的选择百分比来评估雄性Sprague-Dawley大鼠的冲动性决策。LR的延迟在一个会话中以升序(0、4、8、16和32s)改变。
结果：DOI（0.5和1.0mg/kg）增加了冲动性决策，DOI（1.0mg/kg）的作用被5-HT2A受体拮抗剂ketanserin（1.0mg/kg）而不是5-HT2C受体拮抗剂SB-242084（1.0mg/kg）阻断。相反，利苏利特（0.1、0.3和0.5mg/kg）减少了冲动性决策。利苏利特（0.3mg/kg）的作用未被酮色林（1.0mg/kg）拮抗，选择性5-HT1A拮抗剂WAY-100635（1.0mg/kg），或选择性多巴胺D4受体拮抗剂L-745870（1.0mg/kg），但被选择性多巴胺D2/D3受体拮抗剂tiapride（40mg/kg）减毒。
结论：DOI和利苏利特通过不同的受体对冲动决策有对比作用。DOI诱导的冲动增加是由5-HT2A受体介导的，而利脲诱导的冲动抑制受多巴胺D2/D3受体调节。
