David D J, Bourin M, Hascoët M, Colombel M C, Baker G B, Jolliet P
Neurobiologie de lánxiété, Faculté de Médecine, Nantes, France.
Psychopharmacology (Berl). 2001 Feb;153(4):443-9. doi: 10.1007/s002130000588.
A recent study suggested that selective serotonin reuptake inhibitors were inactive in 40-week-old male mice in the mouse forced swimming test, possibly because of alteration of 5-HT1 receptors.
The present study was aimed at investigating the action of various antidepressant drugs in 4- and 40-week-old male mice using the mouse forced swimming test and determining the involvement of 5-HT1A and 5-HT1B receptors mediating the effects.
Different classes of antidepressants [imipramine (tricyclic), maprotiline (noradrenline reuptake inhibitor), venlafaxine (mixed serotonin and noradrenaline reuptake inhibitors), fluvoxamine and sertraline (selective serotonin reuptake inhibitor)] were tested in the same randomised experimental session, alone and in combination with 5-HT1A and 5-HT1B receptor agonists [buspirone (partial 5-HT1A agonist), anpirtoline (5-HT1B agonist)] in the mouse forced swimming test.
All antidepressants were found to be active in the mouse forced swimming test in 4-week-old mice and 40-week-old mice, with the exception of fluvoxamine in the 40-week-old mice. The anti-immobility effect after antidepressant administration was higher in 4-week-old male mice than in 40-week-old male mice. Venlafaxine is the most active antidepressant drug in 40-week-old mice. Prior administration of buspirone (0.06 mg/kg, i.p.) or anpirtoline (1 mg/kg, i.p.) enhanced the antidepressant-like effects in 4-week-old mice (except in the case of sertraline, 8 mg/kg). In elderly mice, only prior administration of buspirone enhanced the antidepressant-like effects of fluvoxamine. A neurochemical study showed that significantly higher serotonin and dopamine concentrations were found in 40-week-old control mice brains than 4-week-old control mice brains but that the noradrenaline concentration is higher in 4-week-old mice.
Tricyclic, noradrenaline reuptake inhibitors and serotonin reuptake inhibitors are more active in 4-week-old mice than 40-week-old mice. Our results suggested that 5-HT1B receptors may be more altered than 5-HT1A receptors in 40-week-old mice.
最近一项研究表明，在小鼠强迫游泳试验中，选择性5-羟色胺再摄取抑制剂对40周龄雄性小鼠无活性，这可能是由于5-HT1受体的改变。
本研究旨在利用小鼠强迫游泳试验研究各种抗抑郁药物在4周龄和40周龄雄性小鼠中的作用，并确定介导这些作用的5-HT1A和5-HT1B受体的参与情况。
在同一随机实验环节中，单独或与5-HT1A和5-HT1B受体激动剂[丁螺环酮（部分5-HT1A激动剂）、安匹托林（5-HT1B激动剂）]联合，对不同种类的抗抑郁药[丙咪嗪（三环类）、马普替林（去甲肾上腺素再摄取抑制剂）、文拉法辛（5-羟色胺和去甲肾上腺素再摄取混合抑制剂）、氟伏沙明和舍曲林（选择性5-羟色胺再摄取抑制剂）]进行小鼠强迫游泳试验。
除40周龄小鼠中的氟伏沙明外，所有抗抑郁药在4周龄和40周龄小鼠的强迫游泳试验中均有活性。给予抗抑郁药后，4周龄雄性小鼠的抗不动效应高于40周龄雄性小鼠。文拉法辛是40周龄小鼠中活性最高的抗抑郁药。预先给予丁螺环酮（0.06mg/kg，腹腔注射）或安匹托林（1mg/kg，腹腔注射）可增强4周龄小鼠的抗抑郁样效应（舍曲林8mg/kg的情况除外）。在老年小鼠中，只有预先给予丁螺环酮可增强氟伏沙明的抗抑郁样效应。一项神经化学研究表明，40周龄对照小鼠脑内5-羟色胺和多巴胺浓度显著高于4周龄对照小鼠，但4周龄小鼠去甲肾上腺素浓度更高。
三环类、去甲肾上腺素再摄取抑制剂和5-羟色胺再摄取抑制剂在4周龄小鼠中比在40周龄小鼠中更具活性。我们的结果表明，在40周龄小鼠中，5-HT1B受体可能比5-HT1A受体改变更大。
