Sumaya I C, Masana M I, Dubocovich M L
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
J Pineal Res. 2005 Sep;39(2):170-7. doi: 10.1111/j.1600-079X.2005.00233.x.
We previously reported an antidepressant-like effect in C3H/HeN mice during the forced swimming test (FST) following treatment with the MT1/MT2 melatonin receptor ligand, luzindole. This study investigated the role melatonin receptors (MT1 and/or MT2) may play in the effect of luzindole in the FST using C3H/HeN mice with a genetic deletion of either MT1 (MT1KO) or MT2 (MT2KO) melatonin receptors. In the light phase (ZT 9-11), luzindole (30 mg/kg, i.p.) significantly decreased immobility during swimming in both wild type (WT) (135.6 +/- 25.3 s, n = 7) and MT(1)KO (132.6 +/- 13.3 s, n = 8) as compared with vehicle-treated mice (WT: 207.1 +/- 6.0 s, n = 7; MT1KO: 209.5 +/- 6.2 s, n = 8) (P < 0.001). In the dark phase (ZT 20-22), luzindole also decreased time of immobility in both WT (89.5 +/- 13.9 s, n = 8) and MT1KO (66.5 +/- 6.4 s, n = 8) mice as compared with the vehicle treated (WT: 193.8 +/- 3.5, n = 6; MT1KO: 176.6 +/- 6.2 s, n = 8) (P < 0.001). Genetic disruption of the MT1 gene did not alter the diurnal rhythm of serum melatonin in MT1KO mice (ZT 9-11: 1.3 +/- 0.6 pg/mL, n = 7; ZT 20-22: 10.3 +/- 1.1 pg/mL, n = 8) as compared with WT (ZT 9-11: 1.4 +/- 0.7 pg/mL; ZT 20-22: 10.6 pg/mL). Swimming did not alter the serum melatonin diurnal rhythm in WT and MT1KO mice. Decreases in immobility of WT and MT1KO mice by luzindole treatment were not affected by gender or age (3 months versus 8 months). In contrast, luzindole did not decrease immobility during the FST in MT2KO mice. We conclude that the antidepressant-like effect of luzindole may be mediated through blockade of MT2 rather than MT1 melatonin receptors.
我们之前报道过，在给予褪黑素MT1/MT2受体配体鲁辛朵治疗后，C3H/HeN小鼠在强迫游泳试验（FST）中呈现出抗抑郁样效应。本研究利用MT1（MT1KO）或MT2（MT2KO）褪黑素受体基因缺失的C3H/HeN小鼠，探究了褪黑素受体（MT1和/或MT2）在鲁辛朵对FST作用中可能发挥的作用。在光照期（ZT 9 - 11），与给予溶剂的小鼠相比（野生型（WT）：207.1±6.0秒，n = 7；MT1KO：209.5±6.2秒，n = 8），鲁辛朵（30毫克/千克，腹腔注射）显著减少了WT（135.6±25.3秒，n = 7）和MT1KO（132.6±13.3秒，n = 8）小鼠游泳时的不动时间（P < 0.001）。在黑暗期（ZT 20 - 22），与给予溶剂的小鼠相比（WT：193.8±3.5秒，n = 6；MT1KO：176.6±6.2秒，n = 8），鲁辛朵也减少了WT（89.5±13.9秒，n = 8）和MT1KO（66.5±6.4秒，n = 8）小鼠的不动时间（P < 0.001）。MT1基因的遗传破坏并未改变MT1KO小鼠血清褪黑素的昼夜节律（ZT 9 - 11：1.3±0.6皮克/毫升，n = 7；ZT 20 - 22：10.3±1.1皮克/毫升，n = 8），与WT（ZT 9 - 11：1.4±0.7皮克/毫升；ZT 20 - 22：10.6皮克/毫升）相比。游泳并未改变WT和MT1KO小鼠血清褪黑素的昼夜节律。鲁辛朵治疗使WT和MT1KO小鼠不动时间减少的情况不受性别或年龄（3个月与8个月）影响。相比之下，鲁辛朵在MT2KO小鼠的FST中并未减少不动时间。我们得出结论，鲁辛朵的抗抑郁样效应可能是通过阻断MT2而非MT1褪黑素受体介导的。
