Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.
Psychopharmacology (Berl). 2013 May;227(2):277-85. doi: 10.1007/s00213-013-2976-1. Epub 2013 Jan 25.
The serotonergic agonist, meta-chlorophenylpiperazine (mCPP), produces inconsistent effects on obsessive-compulsive disorder (OCD) symptoms, perhaps because clinical studies have not utilized a homogenous OCD subgroup of patients.
This study aimed to evaluate mCPP effects on functional components of compulsive checking, using the quinpirole sensitization rat model of OCD.
In study 1, the effects of mCPP were evaluated in quinpirole rats with compulsive checking. Two experimental groups were co-injected with quinpirole (0.125 mg/kg) and mCPP (0.625 or 1.25 mg/kg), while one control group was co-injected with quinpirole (0.125 mg/kg) and saline and the other control group received co-injections of saline. In study 2, mCPP (0, 0.3125, 0.625, and 1.25 mg/kg) was administered repeatedly to naïve rats and induction of compulsive checking evaluated.
mCPP significantly attenuated quinpirole-induced compulsive checking behavior by reducing vigor of checking (indexed by frequency of checking and length of check) and increasing rest after a bout of checking (indexed by time to the next checking bout), but it did not affect focus on the task of checking (indexed by recurrence time of checking and number of stops before returning to check). In naïve rats, mCPP did not induce compulsive behavior, but the highest dose reduced vigor of checking performance compared to saline controls.
mCPP did not exacerbate or induce compulsive checking behavior. Instead, it ameliorated compulsive checking by reducing vigor of checking and increasing post-checking satiety, without affecting focus on checking. Ameliorative effects of mCPP may involve 5HT2A/2C receptors in substantia nigra pars reticulata that inhibit expression of motor vigor.
血清素激动剂，meta-氯苯基哌嗪（mCPP），对强迫症（OCD）症状的影响不一致，这可能是因为临床研究没有利用同质的 OCD 亚组患者。
本研究旨在通过 OCD 的喹吡罗敏化大鼠模型评估 mCPP 对强迫检查的功能成分的影响。
在研究 1 中，评估了 mCPP 在有强迫检查的喹吡罗大鼠中的作用。两个实验组同时注射喹吡罗（0.125mg/kg）和 mCPP（0.625 或 1.25mg/kg），一个对照组同时注射喹吡罗（0.125mg/kg）和生理盐水，另一个对照组接受生理盐水的共注射。在研究 2 中，将 mCPP（0、0.3125、0.625 和 1.25mg/kg）重复给予新生大鼠，并评估其诱发强迫检查的情况。
mCPP 通过减少检查的活力（通过检查的频率和检查的长度来索引）和增加检查后的休息时间（通过下一次检查发作的时间来索引），显著减弱了喹吡罗诱导的强迫检查行为，但不影响检查任务的重点（通过检查的复发时间和返回检查前的停止次数来索引）。在新生大鼠中，mCPP 不会引起强迫行为，但与生理盐水对照组相比，最高剂量会降低检查的活力。
mCPP 既不会加重也不会诱发强迫检查行为。相反，它通过减少检查的活力和增加检查后的满足感来改善强迫检查，而不影响检查的重点。mCPP 的改善作用可能涉及黑质网状部的 5HT2A/2C 受体，抑制运动活力的表达。
