Zohar J, Insel T R, Zohar-Kadouch R C, Hill J L, Murphy D L
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md.
Arch Gen Psychiatry. 1988 Feb;45(2):167-72. doi: 10.1001/archpsyc.1988.01800260081011.
Clomipramine is a potent serotonin reuptake blocker that decreases the symptoms of obsessive-compulsive disorder (OCD). To investigate whether clomipramine treatment in OCD affects brain serotonergic responsiveness, metachlorophenylpiperazine (mCPP), a selective serotonin agonist, and placebo were given under double-blind conditions to nine patients with OCD before and after treatment with clomipramine. Unlike our previous observations of a marked transient increase in obsessional symptoms and anxiety following 0.5 mg/kg of mCPP, readministration of mCPP after four months of treatment with clomipramine did not significantly increase obsessional symptoms and anxiety. Similarly, the hyperthermic effect of mCPP observed before treatment was eliminated after treatment with clomipramine. These findings are consistent with the development of adaptive subsensitivity to the serotonergic agonist mCPP during clomipramine treatment. A similar alteration in the response to endogenous serotonin may mediate clomipramine's antiobsessional effects.
氯米帕明是一种强效的血清素再摄取阻滞剂，可减轻强迫症（OCD）的症状。为了研究氯米帕明治疗强迫症是否会影响大脑血清素反应性，在双盲条件下，对9名强迫症患者在氯米帕明治疗前后给予选择性血清素激动剂间氯苯哌嗪（mCPP）和安慰剂。与我们之前观察到的0.5mg/kg的mCPP给药后强迫症状和焦虑明显短暂增加不同，氯米帕明治疗四个月后再次给予mCPP并没有显著增加强迫症状和焦虑。同样，治疗前观察到的mCPP的体温升高效应在氯米帕明治疗后消失。这些发现与氯米帕明治疗期间对血清素激动剂mCPP的适应性亚敏感性发展一致。对内源性血清素反应的类似改变可能介导氯米帕明的抗强迫作用。
