Saadat Kathryn S, Elliott J Martin, Green A Richard, Moran Paula M
Neuropharmacology Research Group, School of Pharmacy, De Monfort University, The Gateway, Leicester, LE1 9BH, UK.
Psychopharmacology (Berl). 2006 Sep;188(1):75-83. doi: 10.1007/s00213-006-0470-8. Epub 2006 Aug 9.
Evidence suggests that recreational users of (+/-)3,4-methylenedioxymethamphetamine HCl (MDMA, "ecstasy") have cognitive and behavioral deficits and show increased impulsivity consistent with 5-hydroxytryptamine (5-HT) neurotoxicity. MDMA effects on impulsivity in users are difficult to establish being confounded by polydrug use and individual predisposition to impulsivity or behavioral inhibition.
We previously observed a long-term anxiolytic effect of a neurotoxic dose of MDMA on elevated plus maze behavior in Dark Agouti (DA) rats while other strains were reported to show anxiogenesis. We have now examined whether MDMA influences impulsivity producing disinhibited behavior interpretable as anxiolysis.
Impulsivity was measured using an operant visuospatial discrimination procedure. Male DA rats (n = 24) were trained to lever press for food reward in response to a light-stimulus and subsequently required to withhold responding. Correct responses, premature responses, and response latencies were used as measures of accuracy and impulsivity. Trained rats were administered MDMA (5 mg/kg, i.p. at 3-h intervals to a total of three injections). Performance was measured at 3 h and 7, 27, 49, and 80 days posttreatment.
There was a short-term effect of MDMA on the percentage of correct responses at 3 h and day 1 with recovery to control levels by days 7-8 and no significant long-term changes up to day 80. There was no effect of MDMA on premature responses on any of the days measured. MDMA reduced cortical 5-HT content (MDMA 363 +/- 14 ng/g and control 440 +/- 10 ng/g tissue).
These results suggest that impulsivity may not be directly altered by MDMA despite serotonergic neurotoxicity.
有证据表明，使用盐酸（±）3,4-亚甲基二氧甲基苯丙胺（摇头丸，“迷魂药”）进行消遣的人存在认知和行为缺陷，且表现出与5-羟色胺（5-HT）神经毒性一致的冲动性增加。摇头丸对使用者冲动性的影响难以确定，因为多药滥用以及个体的冲动性或行为抑制倾向会造成混淆。
我们之前观察到，神经毒性剂量的摇头丸对黑褐大鼠高架十字迷宫行为具有长期抗焦虑作用，而据报道其他品系则表现出焦虑症。我们现在研究了摇头丸是否会影响冲动性，产生可解释为抗焦虑的去抑制行为。
使用操作性视觉空间辨别程序测量冲动性。雄性黑褐大鼠（n = 24）接受训练，根据光刺激按压杠杆以获取食物奖励，随后要求其抑制反应。正确反应、过早反应和反应潜伏期用作准确性和冲动性的指标。给经过训练的大鼠注射摇头丸（5毫克/千克，腹腔注射，每3小时一次，共注射三次）。在治疗后3小时以及7、27、49和80天测量其行为表现。
摇头丸在3小时和第1天对正确反应百分比有短期影响，到第7 - 8天恢复到对照水平，直至第80天无显著长期变化。在任何测量日，摇头丸对过早反应均无影响。摇头丸降低了皮质5-HT含量（摇头丸组为363±14纳克/克组织，对照组为440±10纳克/克组织）。
这些结果表明，尽管存在5-羟色胺能神经毒性，但摇头丸可能不会直接改变冲动性。
