Pires J G, Silva S R, Futuro-Neto H A
Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Brasil.
Braz J Med Biol Res. 1994 Oct;27(10):2437-41.
Considerable experimental evidence suggests that central dopaminergic (DA) transmission is under serotonergic (5-HTergic) modulation. For instance, neuroleptic-induced catalepsy (NIC) in rodents, a behavior mainly due to blockade of DA receptors in the striatum, can be affected by 5-HTergic manipulation. It has been shown that ligands of 5-HT1A receptors (e.g. buspirone, gepirone) reduce NIC, while 5-HT2 receptor antagonists (e.g. ritanserin) do not affect this phenomenon. However, the role of 5-HT2 receptors in the modulation of NIC is still controversial and there is evidence from behavioral models other than NIC suggesting the existence of functional interaction between the two subtypes of 5-HT receptors. The present study was designed to evaluate the effect of ICI 170,809 (a selective 5-HT2 receptor antagonist) on NIC and to test the possible effect of this drug on the anticataleptic effect of gepirone (GP). Male Wistar rats weighing 300-350 g were used, and each animal (7 per group, 4 groups) was used only once. Catalepsy was induced with haloperidol (H; 1 mg/kg, i.p.) and measured at 30-min intervals by means of a bar test. Animals received either ICI 170,809 (3 mg/kg, i.p.) or 0.9% saline (SL; 0.8 ml, i.p.) 30 min before H. At 110 min after H, the rats received GP (1 mg/kg, i.p.) or SL (0.8 ml, i.p.). GP significantly attenuated NIC (e.g. 739 +/- 106 s vs 1009 +/- 85 s for controls, at 150 min after H), while ICI 170,809 did not significantly affect the phenomenon (e.g. 978 +/-89 s vs 1009 +/- 85 s for controls, at 150 min after H). Pretreatment with ICI 170,809 did not significantly modify the anticataleptic effect of GP (e.g. 617 +/- 90 s vs 739 +/- 106 s for SL-pretreated animals, at 150 min after H). These results confirm reports of the anticataleptic effect of GP and the lack of effect of 5-HT2 receptor antagonists on NIC. Moreover, these data also suggest the absence of functional interactions between central 5-HT1A and 5-HT2 receptors in this model of DA transmission.
大量实验证据表明，中枢多巴胺能（DA）传递受血清素能（5-HT能）调节。例如，啮齿动物中的抗精神病药物诱导的僵住症（NIC），一种主要由于纹状体中DA受体被阻断而产生的行为，会受到5-HT能操作的影响。研究表明，5-HT1A受体的配体（如丁螺环酮、吉哌隆）可减轻NIC，而5-HT2受体拮抗剂（如利坦色林）不会影响此现象。然而，5-HT2受体在调节NIC中的作用仍存在争议，并且有来自NIC以外行为模型的证据表明5-HT受体的两种亚型之间存在功能相互作用。本研究旨在评估ICI 170,809（一种选择性5-HT2受体拮抗剂）对NIC的影响，并测试该药物对吉哌隆（GP）抗僵住症作用的可能影响。使用体重300 - 350 g的雄性Wistar大鼠，每组7只动物，共4组，每只动物仅使用一次。用氟哌啶醇（H；1 mg/kg，腹腔注射）诱导僵住症，并通过棒测试每隔30分钟测量一次。在注射H前30分钟，动物接受ICI 170,809（3 mg/kg，腹腔注射）或0.9%生理盐水（SL；0.8 ml，腹腔注射）。在注射H后110分钟，大鼠接受GP（1 mg/kg，腹腔注射）或SL（0.8 ml，腹腔注射）。GP显著减轻了NIC（例如，在注射H后150分钟，对照组为1009±85秒，而GP组为739±106秒），而ICI 170,809对该现象没有显著影响（例如，在注射H后150分钟，对照组为1009±85秒，ICI 170,809组为978±89秒）。ICI 170,809预处理并未显著改变GP的抗僵住症作用（例如，在注射H后150分钟，SL预处理动物为739±106秒，ICI 170,809预处理动物为617±90秒）。这些结果证实了关于GP抗僵住症作用以及5-HT2受体拮抗剂对NIC无作用的报道。此外，这些数据还表明在该DA传递模型中，中枢5-HT1A和5-HT2受体之间不存在功能相互作用。
