Ninan I, Kulkarni S K
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh.
Indian J Physiol Pharmacol. 1998 Jul;42(3):375-82.
Effect of clozapine on MK-801-induced hyperlocomotion and stereotypy as well as open field behavior was studied. Clozapine (0.1-7.5 mg/kg) dose-dependently blocked MK-801(0.5 mg/kg)-induced stereotypy. Both total and ambulatory responses were blocked by even the lower doses (0.1-0.5 mg/kg) of clozapine. In open field test, clozapine selectively blocked hyperambulation induced by MK-801 (0.1 mg/kg) whereas it potentiated MK-801 (0.1 mg/kg)-induced stereotypy at all the doses used. Haloperidol (0.25 and 0.5 mg/kg) and SCH 23390 (0.5 and 1 mg/kg) showed a dose-dependent effect on MK-801-induced behaviors while sulpiride (25 and 50 mg/kg) failed to modify MK-801-induced open field behavior. This study supports the preferential effect of clozapine on dopamine receptors located in mesolimbic area and further suggests the possibility of using open field behavior induced by MK-801 as a model for studying atypical antipsychotics.
研究了氯氮平对MK-801诱导的活动亢进和刻板行为以及旷场行为的影响。氯氮平(0.1 - 7.5毫克/千克)剂量依赖性地阻断了MK-801(0.5毫克/千克)诱导的刻板行为。即使是较低剂量(0.1 - 0.5毫克/千克)的氯氮平也能阻断总的和走动反应。在旷场试验中,氯氮平选择性地阻断了MK-801(0.1毫克/千克)诱导的过度活动,而在所有使用的剂量下,它都增强了MK-801(0.1毫克/千克)诱导的刻板行为。氟哌啶醇(0.25和0.5毫克/千克)和SCH 23390(0.5和1毫克/千克)对MK-801诱导的行为表现出剂量依赖性作用,而舒必利(25和50毫克/千克)未能改变MK-801诱导的旷场行为。这项研究支持氯氮平对位于中脑边缘区域的多巴胺受体的优先作用,并进一步表明将MK-801诱导的旷场行为用作研究非典型抗精神病药物模型的可能性。