School of Psychology, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom.
Neuropharmacology. 2013 Apr;67:331-6. doi: 10.1016/j.neuropharm.2012.11.012. Epub 2012 Nov 29.
The cognitive effects of MDMA ('Ecstasy') are controversial, particularly in the case of acute administration of low doses. Latent inhibition (LI) refers to the reduction in conditioning to a stimulus that has received non-reinforced pre-exposure, an effect typically abolished by amphetamines and enhanced by antipsychotics. LI enhancement has also been shown using the 5-HT reuptake blocker sertraline. In the present study, the effects of MDMA (6 mg/kg, known to increase 5-HT release) were tested using 10 and 40 pre-exposures to produce weak and strong LI in controls, respectively. MDMA (injected twice, prior to pre-exposure and conditioning) significantly enhanced LI in that the effect was clearly demonstrated after only 10 pre-exposures, when it was absent in the saline controls. On its own such a profile of action would be consistent with a procognitive effect of MDMA mediated by increased availability of 5-HT. However, paradoxically the same MDMA treatment reduced LI in the 40 pre-exposures condition. This component of action is likely attributable to MDMA's actions on catecholaminergic systems and is consistent with other evidence of its adverse effects. Moreover, there were small but significant reductions in 5-HT in medial prefrontal cortex (mPFC) and amygdala assayed 7 days post MDMA administration (2 × 6 mg/kg, 24 h apart).
MDMA（“摇头丸”）的认知效应存在争议，尤其是在急性低剂量给药的情况下。潜伏抑制（LI）是指对已接受非强化预暴露的刺激的条件反射减少，这种效应通常被安非他命类药物消除，并被抗精神病药物增强。使用 5-羟色胺再摄取抑制剂舍曲林也显示出 LI 增强。在本研究中，使用 10 和 40 次预暴露分别在对照组中产生弱和强 LI，测试了 MDMA（6mg/kg，已知增加 5-HT 释放）的作用。MDMA（在预暴露和条件作用之前两次注射）显著增强了 LI，以至于在仅进行 10 次预暴露后就明显表现出这种作用，而在生理盐水对照组中则没有这种作用。这样的作用模式本身就与 MDMA 通过增加 5-HT 的可利用性介导的认知促进作用一致。然而，矛盾的是，相同的 MDMA 处理减少了 40 次预暴露条件下的 LI。这种作用成分可能归因于 MDMA 对儿茶酚胺能系统的作用，这与其他证据表明其具有不良影响一致。此外，在 MDMA 给药 7 天后（2×6mg/kg，间隔 24 小时），在中前额叶皮层（mPFC）和杏仁核中检测到 5-HT 有小但显著的减少。
