Ikram Huma, Samad Noreen, Haleem Darakhshan Jabeen
Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi-75250, Pakistan.
Pak J Pharm Sci. 2007 Jul;20(3):188-95.
Present study was designed to monitor the responsiveness of 5HT (5-Hydroxytryptamine) -2C receptors following the long-term administration of haloperidol in rats. Effects of m-CPP (meta-Chlorophenyl piperazine) were monitored 48 h after withdrawal from repeated (twice a day for 5 week) administration of haloperidol (at the dose of 1 mg/kg). Vacuous chewing movements (VCMs) were monitored on weekly basis. Two days after withdrawal, animals were injected with saline (1 ml/kg of body weight) or m-CPP (3 mg/kg of body weight). Activities in open field and light dark activity box were monitored 15 and 30 min post injection respectively. Animals were then decapitated (4 h post injection) to collect dorsal striatum (DS) samples for the neurochemical analysis by HPLC-EC (High Performance Liquid Chromatography with Electrochemical detection) method. Results from the present study showed significant hypolocomotive effect of m-CPP (p<0.05) in both repeated haloperidol as well as repeated saline injected rats. Neurochemical analysis of DS by HPLC-EC method showed that administration of m-CPP significantly (p<0.05) decreased 5-HIAA (5-Hydroxyindol acetic acid) in repeated haloperidol injected rats. In conclusion, present study provides evidence that 5HT-2C receptors become hypersensitive in a rat model of Tardive Dyskinesia (TD). These findings have potential implication in the treatment of TD and attenuation of EPS induced by typical neuroleptics.
本研究旨在监测大鼠长期服用氟哌啶醇后5-羟色胺（5-HT，5- Hydroxytryptamine）-2C受体的反应性。在反复（每天两次，持续5周）给予氟哌啶醇（剂量为1mg/kg）停药48小时后，监测间氯苯哌嗪（m-CPP，meta-Chlorophenyl piperazine）的作用。每周监测空嚼运动（VCMs）。停药两天后，给动物注射生理盐水（1ml/kg体重）或m-CPP（3mg/kg体重）。分别在注射后15分钟和30分钟监测旷场和明暗活动箱中的活动情况。然后（注射后4小时）将动物断头，收集背侧纹状体（DS）样本，通过高效液相色谱-电化学检测（HPLC-EC，High Performance Liquid Chromatography with Electrochemical detection）法进行神经化学分析。本研究结果显示，m-CPP对反复注射氟哌啶醇以及反复注射生理盐水的大鼠均有显著的运动迟缓作用（p<0.05）。通过HPLC-EC法对DS进行神经化学分析显示，在反复注射氟哌啶醇的大鼠中，给予m-CPP显著降低了5-羟吲哚乙酸（5-HIAA，5-Hydroxyindol acetic acid）（p<0.05）。总之，本研究提供了证据表明在迟发性运动障碍（TD）大鼠模型中5-HT-2C受体变得超敏。这些发现对TD的治疗以及减轻典型抗精神病药物引起的锥体外系反应具有潜在意义。
