Mennini T, Taddei C, Codegoni A, Gobbi M, Garattini S
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Eur J Pharmacol. 1993 Sep 14;241(2-3):255-60. doi: 10.1016/0014-2999(93)90211-y.
Acute noise stress decreased [3H]5-hydroxytryptamine ([3H]5-HT) uptake in synaptosomes from rat hypothalamus, hippocampus and cerebral cortex. The decrease was due to the maximum rate of [3H]5-HT uptake, which peaked 30 min after stress and partly returned to resting values within 4 h, with no changes in affinity (Km values). No changes in [3H]paroxetine binding and basal [3H]5-HT release were found in stressed rats. Tianeptine, given at the dose of 10 mg/kg 1 h before stress, counteracted the noise-induced decrease of 5-HT uptake, since it increased [3H]5-HT uptake in both resting and stressed animals, but did not prevent the rise in plasma corticosterone of stressed rats. Buspirone pretreatment had no effect on [3H]5-HT uptake in resting rats but prevented the noise-induced decrease in [3H]-HT uptake. Diazepam did not modify either the basal or the noise-induced reduction in [3H]5-HT uptake. The evidence that treatments reducing extrasynaptic 5-HT, by increasing its reuptake (tianeptine) or reducing its release (buspirone) in innervated regions are able to modify the stress-induced decrease in 5-HT uptake, further confirms the importance of serotonin in the mechanisms mediating neurochemical responses to stress.
急性噪声应激降低了大鼠下丘脑、海马体和大脑皮层突触体中[3H]5-羟色胺([3H]5-HT)的摄取。这种降低是由于[3H]5-HT摄取的最大速率所致,该速率在应激后30分钟达到峰值,并在4小时内部分恢复到静息值,而亲和力(Km值)没有变化。在应激大鼠中未发现[3H]帕罗西汀结合和基础[3H]5-HT释放有变化。在应激前1小时以10mg/kg的剂量给予噻奈普汀,可抵消噪声诱导的5-HT摄取减少,因为它增加了静息和应激动物中的[3H]5-HT摄取,但并未阻止应激大鼠血浆皮质酮的升高。丁螺环酮预处理对静息大鼠的[3H]5-HT摄取没有影响,但可防止噪声诱导的[3H]-HT摄取减少。地西泮既未改变基础[3H]5-HT摄取,也未改变噪声诱导的[3H]5-HT摄取减少。通过增加突触外5-HT的再摄取(噻奈普汀)或减少其在神经支配区域的释放(丁螺环酮)来降低突触外5-HT的治疗方法能够改变应激诱导的5-HT摄取减少,这一证据进一步证实了5-羟色胺在介导对应激的神经化学反应机制中的重要性。