Redrobe J P, Bourin M, Colombel M C, Baker G B
GIS Médicament, JE 2027 Neurobiologie de l'anxieté, Faculté de Médecine, Nantes, France.
Psychopharmacology (Berl). 1998 Jul;138(1):1-8. doi: 10.1007/s002130050638.
The present study was undertaken to investigate thoroughly the preclinical psychopharmacological profile of venlafaxine, testing a wide range of doses in animal models indicative of antidepressant-like effects. Venlafaxine was found to be active in mouse forced swimming test (at 8, 16, 32 and 64 mg/kg) and to increase spontaneous locomotor activity (at 16, 32 and 64 mg/kg). Venlafaxine antagonised apomorphine-induced (16 mg/kg) hypothermia (at 2, 4, 8, 16, 32 and 64 mg/kg). Pretreatment with PCPA significantly attenuated the anti-immobility effects of venlafaxine (8 and 16mg/kg; P< 0.01) in the mouse forced swimming test. Venlafaxine at a dose of 32 mg/kg remained active, despite PCPA pretreatment. DSP-4 significantly attenuated the anti-immobility effects of venlafaxine (16 mg/kg; P < 0.05), whereas venlafaxine at 32 mg/kg remained active, despite DSP-4 pretreatment. Venlafaxine was active in the forced swimming test when administered at sub-effective doses in combination with (+/-) pindolol (venlafaxine: 1 and 2 mg/kg), RU 24969 (venlafaxine: 1, 2 and 4 mg/kg), 8-OH-DPAT (venlafaxine: 4 mg/kg), clonidine (venlafaxine: 1, 2 and 4 mg/kg), lithium (venlafaxine: 1, 2, and 4 mg/kg) and quinine (venlafaxine: 1 and 2 mg/kg). Prior administration with NAN-190 antagonised the anti-immobility effects of venlafaxine (8, 16 and 32 mg/kg). Interaction studies did not induce changes in locomotor activity. The results of the present study indicated that, at low doses, venlafaxine inhibited serotonin reuptake, while at higher doses it inhibited both serotonin and noradrenaline reuptake.
本研究旨在全面调查文拉法辛的临床前精神药理学特征，在指示抗抑郁样效应的动物模型中测试了广泛的剂量范围。发现文拉法辛在小鼠强迫游泳试验中具有活性（剂量为8、16、32和64mg/kg），并可增加自发运动活性（剂量为16、32和64mg/kg）。文拉法辛拮抗阿扑吗啡诱导的（16mg/kg）体温过低（剂量为2、4、8、16、32和64mg/kg）。在小鼠强迫游泳试验中，用对氯苯丙氨酸（PCPA）预处理可显著减弱文拉法辛（8和16mg/kg；P<0.01）的抗不动效应。尽管进行了PCPA预处理，32mg/kg剂量的文拉法辛仍具有活性。双硫仑（DSP-4）显著减弱了文拉法辛（16mg/kg；P<0.05）的抗不动效应，而尽管进行了DSP-4预处理，32mg/kg剂量的文拉法辛仍具有活性。当以亚有效剂量与（±）吲哚洛尔（文拉法辛：1和2mg/kg）、RU 24969（文拉法辛：1、2和4mg/kg）、8-羟基二丙胺基四氢萘（8-OH-DPAT，文拉法辛：4mg/kg）、可乐定（文拉法辛：1、2和4mg/kg）、锂盐（文拉法辛：1、2和4mg/kg）和奎宁（文拉法辛：1和2mg/kg）联合给药时，文拉法辛在强迫游泳试验中具有活性。预先给予NAN-190可拮抗文拉法辛（8、16和32mg/kg）的抗不动效应。相互作用研究未引起运动活性的变化。本研究结果表明，在低剂量时，文拉法辛抑制5-羟色胺再摄取，而在高剂量时，它同时抑制5-羟色胺和去甲肾上腺素再摄取。
