Rénéric Jean-Philippe, Bouvard Manuel, Stinus Luis
Laboratoire de Neuropsychobiologie des Désadaptations, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541, BP31, Université Bordeaux II, 33076 Bordeaux Cedex, France.
Behav Brain Res. 2002 Nov 15;136(2):521-32. doi: 10.1016/s0166-4328(02)00203-6.
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.
(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 microg/kg) with 10 mg/kg fluoxetine.
(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.
Chronic enhancement of NA-transmission alters NA-system-mediated inhibition of 5-HT-induced behaviour in the FST, which may involve alpha(2)-receptors.
大鼠强迫游泳试验（FST）可区分选择性5-羟色胺（5-HT）和选择性去甲肾上腺素（NA）再摄取抑制剂，这两种抑制剂分别增加游泳和攀爬行为。然而，NA系统介导的对5-HT诱导游泳的抑制作用会阻止5-HT/NA双重再摄取抑制同时产生攀爬和游泳行为。由于在抑郁症治疗中会发生适应性神经化学过程，我们研究了长期抗抑郁治疗对这些相互作用的影响。
（1）选择性[氟西汀：10毫克/千克；地昔帕明：10毫克/千克]和非选择性[米那普明：40毫克/千克；米氮平：20毫克/千克]抗抑郁药在16天内进行亚急性（3次注射）和慢性（17次注射）给药。（2）在预先用慢性地昔帕明（每天10毫克/千克，共14天）预处理的大鼠中给予亚急性氟西汀-地昔帕明组合（10-10毫克/千克）。（3）通过将α（2）-受体激动剂可乐定（5、10、20、200微克/千克）与10毫克/千克氟西汀联合使用，进一步研究NA系统介导的相互作用。
（1）长期使用氟西汀或地昔帕明治疗不会改变其亚急性给药产生的行为反应。（2）相比之下，亚急性米那普明仅增加攀爬行为，而慢性米那普明产生更大的抗不动作用，并增加攀爬和游泳行为。同样，氟西汀-地昔帕明组合仅产生攀爬行为，但在预先用慢性地昔帕明治疗的动物中会增加攀爬和游泳行为。慢性而非亚急性米氮平增加游泳行为。（3）可乐定剂量依赖性地拮抗氟西汀诱导的抗不动作用和游泳行为。
NA传递的慢性增强改变了FST中NA系统介导的对5-HT诱导行为的抑制作用，这可能涉及α（2）-受体。
