Vollenweider F X, Remensberger S, Hell D, Geyer M A
Psychiatric University Hospital Zürich, Research Department, Switzerland.
Psychopharmacology (Berl). 1999 Apr;143(4):365-72. doi: 10.1007/s002130050960.
Prepulse inhibition of acoustic startle refers to the reduction in the startle response when the startling stimulus is preceded by a weak prepulse stimulus. This phenomenon provides an operational measure of sensorimotor gating that has been found to be reduced in patients with schizophrenia and rats treated with serotonin agonists or serotonin releasers.
In this study, we compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in laboratory rats and healthy human volunteers. In particular, we investigated whether MDMA disrupts PPI in humans as observed in animal studies.
Rats were tested after placebo and MDMA in a counterbalanced order at an interval of 1 week, with separate groups of rats being used for each dose of MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after no injections and retested 2 h later, 10 min after a subcutaneous injection of placebo or MDMA. For the human study, a placebo-controlled within-subject design and double-blind procedures were used. Subjects were examined twice at a 2 to 4 week interval after either placebo or drug administration (order being counterbalanced). On each test day, subjects underwent baseline testing including psychological and PPI measures. Ninety minutes later, subjects received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during the peak of behavioral effects of MDMA.
As expected, MDMA decreased prepulse inhibition in a dose-related fashion in rats. In contrast, a typical recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in subjects experiencing robust psychological effects.
This surprising disparity between the effects of the drug in rats and humans may reflect a species-specific difference in the mechanism of action of MDMA or in the behavioral expression of a similar pharmacological effect, or both.
听觉惊吓的前脉冲抑制是指当惊吓刺激之前出现一个弱的前脉冲刺激时，惊吓反应的减弱。这种现象提供了一种感觉运动门控的操作测量方法，已发现精神分裂症患者以及用血清素激动剂或血清素释放剂治疗的大鼠中该测量值降低。
在本研究中，我们比较了血清素释放剂摇头丸（MDMA）对实验室大鼠和健康人类志愿者前脉冲抑制的影响。特别是，我们调查了MDMA是否如在动物研究中观察到的那样破坏人类的前脉冲抑制。
大鼠在接受安慰剂和MDMA后以平衡顺序进行测试，间隔1周，每组大鼠用于每种剂量的MDMA（1.7、5.4和17.0mg/kg）。在每个测试日，大鼠首先在未注射的情况下进行测试，并在2小时后、皮下注射安慰剂或MDMA后10分钟再次测试。对于人体研究，采用了安慰剂对照的受试者内设计和双盲程序。受试者在服用安慰剂或药物后以2至4周的间隔接受两次检查（顺序平衡）。在每个测试日，受试者接受包括心理和前脉冲抑制测量在内的基线测试。90分钟后，受试者接受安慰剂或MDMA（1.7mg/kg口服），并在MDMA行为效应高峰期75分钟后再次测试。
正如预期的那样，MDMA以剂量相关的方式降低了大鼠的前脉冲抑制。相比之下，典型的娱乐剂量MDMA（1.7mg/kg，口服）增加了出现强烈心理效应的受试者的前脉冲抑制。
药物在大鼠和人类中的作用效果之间这种惊人的差异可能反映了MDMA作用机制或类似药理效应行为表达中的物种特异性差异，或两者兼而有之。
