Phencyclidine-induced behaviour in mice prevented by methylene blue
Phencyclidine-induced behaviour in mice prevented by methylene blue
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DOI：
10.1111/j.1742-7843.2004.pto940203.x
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发表时间：
2004-02-01
影响因子：
3.1
通讯作者：
Svensson, L
中科院分区：
文献类型：
--
作者：
Klamer, D;Engel, JA;Svensson, L
精神分裂症是一个主要的公共卫生问题，影响全球约1%的人口。精神分裂症样症状可由苯环利定（PCP）在人类中诱导，苯环利定是一种具有明显拟精神病特性的药物。苯环己哌啶破坏啮齿动物的声惊吓的前脉冲抑制，这一措施也被证明是在精神分裂症患者中被破坏。这种作用被一氧化氮合酶（NOS）抑制剂阻断，表明一氧化氮在苯环利定的这种作用中起重要作用。亚甲蓝是一种鸟苷酸环化酶和一氧化氮合酶抑制剂，在精神分裂症的治疗中作为常规抗精神病药的辅助治疗显示出治疗价值。本研究的目的是研究苯环利定（4 mg/kg）诱导的前脉冲抑制的破坏是否会受到亚甲蓝（50或100 mg/kg）的影响。此外，研究了亚甲蓝（50 mg/kg）对苯环利定（4 mg/kg）诱导的过度运动的影响。目前的研究表明，苯环利定很容易破坏前脉冲抑制小鼠不影响脉冲单独试验。还发现亚甲蓝以剂量相关的方式防止苯环利定引起的前脉冲抑制的降低。此外，苯环利定引起的自发活动的增加减少了预处理与亚甲蓝。本研究的结果进一步支持了一氧化氮合酶/鸟苷酸环化酶途径参与苯环利定的药理学和行为学作用的建议。由于苯环利定也发挥拟精神病特征，干扰一氧化氮合酶/鸟苷酸环化酶途径的药物在治疗精神分裂症中也可能具有治疗价值。
Schizophrenia is a major public health problem that affects approximately 1% of the population worldwide. Schizophrenia-like symptoms can be induced in humans by phencyclidine (PCP), a drug with marked psychotomimetic properties. Phencyclidine disrupts prepulse inhibition of acoustic startle in rodents, a measure which has also been shown to be disrupted in schizophrenic patients. This effect is blocked by nitric oxide synthase (NOS) inhibitors, suggesting that nitric oxide plays an important role in this effect of phencyclidine. Methylene blue, a guanylate cyclase and nitric oxide syntase inhibitor, has shown therapeutic value as an adjuvant to conventional antipsychotics in the therapy of schizophrenia. The aim of the present study was to investigate if phencyclidine-(4 mg/kg)induced disruption of prepulse inhibition could be affected by methylene blue (50 or 100 mg/kg) in mice. Furthermore, the effect of methylene blue (50 mg/kg) on phencyclidine-(4 mg/kg)induced hyperlocomotion was investigated. The present study shows that phencyclidine readily disrupts prepulse inhibition in mice without affecting pulse-alone trials. It was also found that methylene blue prevents the decrease in prepulse inhibition caused by phencyclidine in a dose-related manner. Furthermore, the increase in locomotor activity caused by phencyclidine was reduced by pretreatment with methylene blue. The results from the present study further support the suggestion that the nitric oxide synthase/guanylate cyclase pathway is involved in pharmacological and behavioural effects of phencyclidine. Since phencyclidine as well exerts psychotomimetic characteristics, agents that interfere with the nitric oxide synthase/guanylate cyclase pathway may be of therapeutic value also in the treatment of schizophrenia.