Effect of 1-(m-chlorophenyl)piperazine and 1-(m-trifluoromethylphenyl)piperazine on locomotor activity.
Effect of 1-(m-chlorophenyl)piperazine and 1-(m-trifluoromethylphenyl)piperazine on locomotor activity.
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发表时间：
1989-04
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通讯作者：
I. Lucki;H. R. Ward;A. Frazer
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作者：
I. Lucki;H. R. Ward;A. Frazer
哌嗪型5-羟色胺(5-HT)激动剂1-(间三氟甲基苯基)哌嗪(TFMPP)、1-(间氯苯基)-哌嗪(m-CPP)、1-(对氯苯基)哌嗪(p-CPP)和MK-212[6-氯-2-(1-哌嗪基)吡嗪]对大鼠自发活动有剂量依赖性的抑制作用。预先给予5-羟色胺拮抗剂美特灵、甲基丝氨酸或米安色林，但不阻断选择性5-羟色胺或儿茶酚胺拮抗剂，可阻断TFMPP引起的活动降低，提示5-羟色胺受体的兴奋参与了这种行为效应。注射TFMPP、m-CPP或MK-212的大鼠，除中毒剂量外，未观察到5-羟色胺受体兴奋的其他行为体征，如5-羟色胺行为综合征或摇头行为。5-羟色胺神经传递的长期变化改变了哌嗪激动剂减少大鼠运动活动的能力。静脉注射对5-羟色胺神经元的破坏作用。注射神经毒素5，7-二羟色胺可增强m-CPP抑制行走行为的能力。另一方面，通过给予单胺氧化酶抑制剂苯乙肼或烟酰胺7天来增加5-羟色胺的含量，降低了m-CPP抑制运动活动的能力。急性给予单胺氧化酶抑制剂，或长期给予其他抗抑郁药，如去甲基米帕明或伊普利多尔，都不能改变m-CPPs的活性抑制效应。这些研究表明，5-羟色胺神经传递的慢性变化会产生代偿性变化，从而改变对这些哌嗪激动剂的行为反应。结合其他证据表明TFMPP和m-CPP都是5-HT1B和5-HT1C受体的激动剂，TFMPP和m-CPP对运动活动的影响可能与选择性激活5-HT1C或5-HT1B受体有关。
The piperazine-type 5-hydroxytryptamine (5-HT) agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP), 1-(m-chlorophenyl)-piperazine (m-CPP), 1-(p-chlorophenyl)piperazine (p-CPP) and MK-212 [6-chloro-2-(1-piperazinyl)pyrazine], produced a dose-dependent suppression of spontaneous ambulatory behavior in rats. Pretreatment with the 5-HT antagonists metergoline, methysergide or mianserin, but not selective 5-HT2 or catecholamine antagonists, blocked the reduction of activity caused by TFMPP suggesting that the stimulation of 5-HT receptors was involved in causing this behavioral effect. Other behavioral signs of 5-HT receptor stimulation, such as the 5-HT behavioral syndrome or head-shaking behavior, were not observed in rats injected with TFMPP, m-CPP or MK-212 except at toxic doses. The ability of piperazine agonists to reduce locomotor activity in rats was altered by long-term changes in 5-HT neurotransmission. The destruction of 5-HT neurons by i.v.t. injection of the neurotoxin 5,7-dihydroxytryptamine potentiated the ability of m-CPP to inhibit ambulatory behavior. On the other hand, elevating 5-HT content by administering the monoamine oxidase inhibitors phenelzine or nialamide for 7 days reduced the ability of m-CPP to suppress locomotor activity. Acute administration of the monoamine oxidase inhibitors, or chronic administration of other antidepressants such as desmethylimipramine or iprindole, failed to alter m-CPPs activity-suppressant effects. These studies suggest that chronic changes in 5-HT neurotransmission produce compensatory changes which alter the behavioral response to these piperazine agonists. Taken together with other evidence that both TFMPP and m-CPP are agonists at 5-HT1B and 5-HT1C receptors, the effects of TFMPP and m-CPP on locomotor activity may be associated with the selective activation of 5-HT1C, or possibly 5-HT1B, receptors.