Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol
Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol
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DOI：
10.1007/s00213-007-0701-7
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发表时间：
2007-06-01
影响因子：
3.4
通讯作者：
Robbins, Trevor W.
中科院分区：
文献类型：
--
作者：
Eagle, Dawn M.;Tufft, Miles R. A.;Robbins, Trevor W.
停止信号反应时间（SSRT）任务测量对已经启动的反应的抑制，即停止的能力。“冲动”的人类受试者，例如患有注意力缺陷和多动障碍（ADHD）的受试者，具有较长的SSRT。无论是在正常受试者还是多动症受试者中，SSRT和GoRT都可能对d-苯丙胺、哌甲酯和莫达非尼等药物敏感。研究莫达非尼（3、10、30和100 mg/kg）和哌甲酯（0.3、1.0和3.0 mg/kg）对大鼠SSRT任务表现的影响。使用混合D1/D2多巴胺受体拮抗剂顺式氟哌噻吨，研究多巴胺受体在这些药物作用中的可能作用。莫达非尼显著降低SSRT，对GoRT影响不大，但仅在基线SSRT缓慢的大鼠中。莫达非尼没有改变快速SSRT。哌甲酯降低所有大鼠的GoRT。然而，哌甲酯对SSRT有基线依赖性影响，在慢反应者中降低SSRT，但在快反应者中增加SSRT。顺式氟噻吨（0.01，0.04和0.125 mg/kg）对SSRT没有影响，但在较高剂量下增加了GoRT。在最低剂量（0.01 mg/kg）下，顺式氟哌噻吨未能破坏莫达非尼或哌甲酯的SSRT降低作用，而在0.04 mg/kg下，哌甲酯拮抗顺式氟哌噻吨依赖性GoRT增加，但莫达非尼不拮抗顺式氟哌噻吨依赖性GoRT增加。
The stop-signal reaction time (SSRT) task measures inhibition of a response that has already been initiated, i.e. the ability to stop. 'Impulsive' human subjects, e.g. with attention deficit and hyperactivity disorder (ADHD), have longer SSRTs. Both SSRT and go-trial reaction time (GoRT) may be sensitive to drugs such as d-amphetamine, methylphenidate and modafinil, both in normal subjects and those with ADHD.To investigate the effects of modafinil (3, 10, 30 and 100 mg/kg) and methylphenidate (0.3, 1.0 and 3.0 mg/kg) on SSRT task performance in the rat. To investigate the possible contribution of dopamine receptors in the action of these drugs using the mixed D1/D2 dopamine receptor antagonist cis-flupenthixol.Modafinil significantly decreased SSRT with little effect on GoRT but only in rats with slow baseline SSRTs. Fast SSRTs were not changed by modafinil. Methylphenidate decreased GoRTs of all rats. However, methylphenidate had baseline-dependent effects on SSRT, decreasing SSRT in slow responders but increasing SSRT in fast responders. Cis-flupenthixol (0.01, 0.04 and 0.125 mg/kg) had no effects on SSRT but increased GoRT at higher doses. At the lowest dose (0.01 mg/kg), cis-flupenthixol failed to disrupt the SSRT-decreasing effects of either modafinil or methylphenidate, whereas at 0.04 mg/kg, the cis-flupenthixol-dependent increase in GoRT was antagonised by methylphenidate but not by modafinil.This evidence supports a hypothesis that stop and go processes are under control of distinct neurochemical mechanisms.