Silva S R, Futuro-Neto H A, Pires J G
Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, ES, Brazil.
Neuropharmacology. 1995 Jan;34(1):97-9. doi: 10.1016/0028-3908(94)00146-j.
Typical neuroleptics (e.g. haloperidol) can induce a cataleptic state in rodents by means of striatal DA receptor blockade. It has been shown that drugs which influence central serotonergic (5-HTergic) mechanisms can modify neuroleptic-induced catalepsy, suggesting that dopaminergic transmission is under 5-HTergic modulation. The aim of this study was to examine the effects of bemesetron and granisetron, two selective 5-HT3 receptor antagonists, on this catalepsy in mice. Catalepsy was induced with haloperidol (1.5 mg/kg, i.p.) and measured at 30-min intervals by means of a bar test. Drugs (or saline, for the controls) were injected i.p. 20 min before haloperidol, with each animal used only once. Bemesetron significantly reduced catalepsy at a dose of 1 mg/kg, whilst 10 mg/kg potentiated the phenomenon and 0.1 mg/kg was found to be without effect. Granisetron inhibited catalepsy at doses of 0.04 and 0.1 mg/kg while 4 mg/kg of the antagonist significantly increased the duration of catalepsy. These data suggest that 5-HT3 receptors play a role in neuroleptic-induced catalepsy. Considering the high affinities of both antagonists for 5-HT3 receptors, it is tempting to speculate that the potentiation of catalepsy by high doses of them is due to non 5-HT3 receptor mechanisms.
典型的抗精神病药物（如氟哌啶醇）可通过阻断纹状体多巴胺受体在啮齿动物中诱发僵住症状态。已有研究表明，影响中枢血清素能（5-羟色胺能）机制的药物可改变抗精神病药物诱发的僵住症，这表明多巴胺能传递受5-羟色胺能调节。本研究的目的是研究两种选择性5-羟色胺3受体拮抗剂倍他司琼和格拉司琼对小鼠这种僵住症的影响。用氟哌啶醇（1.5毫克/千克，腹腔注射）诱发僵住症，并通过棒试验每隔30分钟测量一次。在注射氟哌啶醇前20分钟腹腔注射药物（或生理盐水作为对照），每只动物只使用一次。倍他司琼在1毫克/千克的剂量下可显著减轻僵住症，而10毫克/千克则增强了这一现象，0.1毫克/千克则无效果。格拉司琼在0.04和0.1毫克/千克的剂量下可抑制僵住症，而4毫克/千克的拮抗剂则显著增加了僵住症的持续时间。这些数据表明5-羟色胺3受体在抗精神病药物诱发的僵住症中起作用。考虑到两种拮抗剂对5-羟色胺3受体的高亲和力，很容易推测高剂量的它们增强僵住症是由于非5-羟色胺3受体机制。
