Koek W, Colpaert F C
Neurobiology Division, Fondax, Puteaux, France.
J Pharmacol Exp Ther. 1993 Oct;267(1):181-91.
Methylphenidate (MPD) increased in rats the incidence of sniffing, rearing and locomotion, and this along dose-response curves that had an inverted U-shape; at 40 mg/kg, MPD exclusively induced stereotyped gnawing, which was inhibited by neuroleptics. However, as gnawing induced by 40 mg/kg MPD was inhibited in a dose-dependent manner, other responses (i.e., sniffing, rearing and locomotion) appeared. Higher doses of neuroleptics also inhibited these latter responses, so that the behavior of the MPD-treated animals became similar to that of normal controls. Only some nonsedative neuroleptics appeared able to normalize the behavior of MPD-treated rats at doses that induced neither complete behavioral suppression nor adverse effects. The neuroleptics differed markedly, however, in terms of the relative doses at which they 1) inhibited gnawing, 2) inhibited the other effects of MPD and 3) induced complete behavioral suppression and/or adverse effects. This variation among neuroleptics, which appears to represent a novel aspect of their ability to antagonize behavioral effects of central nervous system stimulants, may be based on differences in the extent to which they exert agonist activity at dopamine receptors. Assuming that MPD-induced behaviors model the positive symptoms of schizophrenia, it may be hypothesized that the differences among the neuroleptics observed here provide an indication of their efficacy to reduce positive symptoms in schizophrenics.
哌甲酯（MPD）可增加大鼠嗅探、竖身和活动的发生率，且呈倒U形剂量反应曲线；在40mg/kg时，MPD仅诱导刻板啃咬行为，该行为可被抗精神病药物抑制。然而，由于40mg/kg MPD诱导的啃咬行为呈剂量依赖性抑制，其他反应（即嗅探、竖身和活动）出现。更高剂量的抗精神病药物也抑制了这些后期反应，因此接受MPD治疗的动物的行为变得与正常对照相似。只有一些非镇静性抗精神病药物似乎能够在既不引起完全行为抑制也不产生不良反应的剂量下使接受MPD治疗的大鼠的行为正常化。然而，抗精神病药物在以下相对剂量方面存在显著差异：1）抑制啃咬行为；2）抑制MPD的其他效应；3）引起完全行为抑制和/或不良反应。抗精神病药物之间的这种差异似乎代表了它们拮抗中枢神经系统兴奋剂行为效应能力的一个新方面，可能基于它们在多巴胺受体上发挥激动剂活性程度的差异。假设MPD诱导的行为模拟了精神分裂症的阳性症状，可以推测，此处观察到的抗精神病药物之间的差异表明了它们减轻精神分裂症患者阳性症状的疗效。
