Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
Behav Brain Res. 2013 Jan 1;236(1):157-165. doi: 10.1016/j.bbr.2012.08.048. Epub 2012 Sep 4.
Recent studies suggest a potential role for 5-hydroxytryptamine(6) (5-HT(6)) receptors in the regulation of addictive behavior. In the present study, our aim was to investigate whether the novel highly selective 5-HT(6) receptor antagonist compound (CMP) 42 affected nicotine and ethanol seeking behavior in Wistar rats. We have also studied whether CMP 42 had beneficial effects in a model of impulse control, as measured in the 5-choice serial reaction time task (5-CSRTT). Rats were trained to nose poke to receive intravenous infusions of nicotine or an ethanol drop. CMP 42 (3-30 mg/kg intraperitoneally, i.p.) was administered to investigate the effects on nicotine self-administration. Rats were also tested for cue-induced reinstatement of nicotine and ethanol seeking. In addition, the effects of CMP 42 were studied on the number of anticipatory responses in the 5-CSRTT. CMP 42 was effective in reducing nicotine self-administration and reinstatement of nicotine seeking at a dose of 30 mg/kg (i.p.). CMP 42 was also effective in reducing reinstatement of ethanol seeking (30 mg/kg i.p.). In contrast, CMP 42 did not affect anticipatory responding at doses tested, indicating no effects on impulse control. These results add to a body of evidence implicating the 5-HT(6) receptor as a viable target for the control of drug abuse. Specifically, we demonstrated for the first time effects on nicotine self-administration and on nicotine and ethanol reinstatement. Further, these effects are probably not mediated by effects on impulse control.
最近的研究表明，5-羟色胺（6）（5-HT（6））受体在调节成瘾行为方面可能发挥作用。本研究旨在探讨新型高选择性 5-HT（6）受体拮抗剂化合物（CMP）42 是否会影响 Wistar 大鼠的尼古丁和乙醇觅药行为。我们还研究了 CMP 42 是否在冲动控制模型中具有有益作用，如在 5 选择连续反应时间任务（5-CSRTT）中测量的。大鼠被训练为鼻探测以接受静脉内输注尼古丁或乙醇滴。给予 CMP 42（3-30 mg/kg 腹腔内，i.p.）以研究其对尼古丁自我给药的影响。还测试了大鼠对尼古丁和乙醇觅药的线索诱导复吸的影响。此外，还研究了 CMP 42 对 5-CSRTT 中预期反应次数的影响。CMP 42 可有效降低尼古丁自我给药和尼古丁觅药的复吸，剂量为 30 mg/kg（i.p.）。CMP 42 还可有效降低乙醇觅药的复吸（30 mg/kg i.p.）。相反，在测试剂量下，CMP 42 对预期反应没有影响，表明对冲动控制没有影响。这些结果增加了 5-HT（6）受体作为控制药物滥用的可行靶点的证据。具体来说，我们首次证明了 CMP 42 对尼古丁自我给药以及尼古丁和乙醇复吸的影响。此外，这些作用可能不是通过对冲动控制的影响介导的。
