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首页> 外文期刊>Behavioural Brain Research: An International Journal >In the rat forced swimming test, chronic but not subacute administration of dual 5-HT/NA antidepressant treatments may produce greater effects than selective drugs
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In the rat forced swimming test, chronic but not subacute administration of dual 5-HT/NA antidepressant treatments may produce greater effects than selective drugs

机译：在大鼠强迫游泳试验中，与5-HT / NA双重抗抑郁药联合治疗，但非亚急性的慢性治疗可能会产生比选择性药物更大的疗效

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The rat forced swimming test (FST) distinguishes selective serotonin (5-HT) and selective noradrenaline (NA) reuptake-inhibitors, which respectively increase swimming and climbing behaviours. However, NA-system-mediated inhibition of 5-HT-induced swimming prevents dual 5-HT/NA reuptake-inhibition to produce concurrently climbing with swimming. Since adaptative neurochemical processes occur in the treatment of depression, we examined the influence of long-term antidepressant treatment on these interactions. Methods: (1) Selective [fluoxetine: 10 mg/kg; desipramine: 10 mg/kg] and non-selective [milnacipran: 40 mg/kg; mirtazapine: 20 mg/kg] antidepressants were administered subacutely (3inj) and chronically (17inj) over 16 days. (2) A subacute fluoxetine-desipramine combination (10-10 mg/kg) was administered in rats that were pre-treated with chronic-desipramine (10 mg/ kg per day, 14 days). (3) NA-system-mediated interactions were further examined by combining the alpha_2-receptor agonist clonidine (5, 10, 20, 200 ug/kg) with 10 mg/kg fluoxetine. Results: (1) Long-term treatment with either fluoxetine or desipramine does not modify the behavioural response produced by their subacute administration. (2) In contrast, whereas subacute-milnacipran increases climbing solely, chronic-milnacipran produces greater anti-immobility effects and increases both climbing and swimming behaviours. Similarly, the fluoxetine-desipramine combination produces climbing solely, but increases both climbing and swimming behaviours in animals pre-treated with chronic-desipramine. Chronic but not subacute-mirtazapine increases swimming behaviour. (3) clonidine dose-dependently antagonizes fluoxetine-induced anti-immobility effects and swimming behaviour. Conclusions: Chronic enhancement of NA-transmission alters NA-system-mediated inhibition of 5-HT-induced behaviour in the FST, which may involve alpha_2-receptors.
机译：大鼠强制游泳试验（FST）区分选择性5-羟色胺（5-HT）和选择性去甲肾上腺素（NA）再摄取抑制剂，它们分别增加游泳和攀爬行为。但是，NA系统介导的5-HT诱导的游泳抑制作用会阻止双重5-HT / NA再摄取抑制作用，从而在游泳时同时进行攀爬。由于适应性神经化学过程发生在抑郁症的治疗中，因此我们研究了长期抗抑郁治疗对这些相互作用的影响。方法：（1）选择性[氟西汀：10 mg / kg;地昔帕明：10 mg / kg]和非选择性[米那普仑：40 mg / kg;米氮平：20毫克/千克抗抑郁药在16天内分次（3inj）和长期（17inj）给药。 （2）在用慢性地昔帕明（每天10mg / kg，14天）预处理的大鼠中给予亚急性氟西汀-地昔帕明组合（10-10mg / kg）。 （3）通过将α_2受体激动剂可乐定（5、10、20、200 ug / kg）与10 mg / kg氟西汀组合，进一步检查了NA系统介导的相互作用。结果：（1）长期使用氟西汀或地昔帕明治疗不会改变亚急性给药产生的行为反应。 （2）相反，亚急性米那普仑仅增加爬坡，而慢性米那普仑则具有更大的抗固定作用，并且增加了爬山和游泳行为。类似地，氟西汀-地昔帕明的组合仅产生爬升，但是增加了用慢性地昔帕明预处理的动物的爬升和游泳行为。慢性但非急性米氮平增加了游泳行为。 （3）可乐定剂量依赖性地拮抗氟西汀诱导的抗固定作用和游泳行为。结论：慢性NA传递的增强改变了NA系统介导的对5-HT诱导的FST行为的抑制，这可能涉及α_2受体。

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