Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2012;64(6):1391-9. doi: 10.1016/s1734-1140(12)70936-2.
Several clinical reports have postulated a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants in treatment-resistant depression.
The present study aimed to examine the effect of treatment with fluoxetine or mirtazapine, given separately or jointly with risperidone, on active behavior and plasma corticosterone level in male Wistar rats subjected to the forced swim test (FST).
The obtained results showed that fluoxetine (5 mg/kg), mirtazapine (5 and 10 mg/kg) or risperidone (0.05 and 0.1 mg/kg) did not change the active behavior of rats in the FST. However, co-treatment with fluoxetine (10 mg/kg) and risperidone (0.1 mg/kg) induced an antidepressant-like effect in that test because it significantly increased the swimming time and decreased the immobility time, while combined treatment with mirtazapine at 5 and 10 mg/kg and risperidone at 0.05 and 0.1 mg/kg evoked a significant increase in the swimming time and also climbing, and decreased the immobility time. WAY 100635 (a 5-HT(1A) receptor antagonist) at a dose of 0.1 mg/kg inhibited the antidepressant-like effect induced by co-administration of fluoxetine or mirtazapine and risperidone. Active behavior in that test did not reflect an increase in general activity, since combined treatment with fluoxetine or mirtazapine and risperidone failed to enhance the exploratory activity of rats. Co-treatment with fluoxetine or mirtazapine and risperidone did not reduce the stress-induced increase in plasma corticosterone concentration in animals subjected to the FST.
The obtained results indicate that risperidone applied in a low dose enhances the antidepressant-like activity of fluoxetine and mirtazapine in the FST (but does not normalize the stress-induced increase in corticosterone level in these rats), and that 5-HT(1A) receptors may play some role in these effects.
有几项临床报告推测，在治疗抵抗性抑郁症患者时，在持续使用抗抑郁药的基础上，添加低剂量利培酮可能会产生有益的效果。
本研究旨在检验氟西汀或米氮平单独或联合利培酮治疗对强迫游泳试验（FST）中雄性 Wistar 大鼠的主动行为和血浆皮质酮水平的影响。
研究结果表明，氟西汀（5mg/kg）、米氮平（5 和 10mg/kg）或利培酮（0.05 和 0.1mg/kg）均未改变 FST 中大鼠的主动行为。然而，氟西汀（10mg/kg）和利培酮（0.1mg/kg）联合治疗在该测试中诱导出抗抑郁样作用，因为它显著增加了游泳时间并减少了不动时间，而米氮平（5 和 10mg/kg）和利培酮（0.05 和 0.1mg/kg）联合治疗则显著增加了游泳时间和攀爬次数，同时减少了不动时间。WAY 100635（5-HT1A 受体拮抗剂）的剂量为 0.1mg/kg，可抑制氟西汀或米氮平联合利培酮引起的抗抑郁样作用。该测试中的主动行为并未反映出一般活动的增加，因为联合使用氟西汀或米氮平与利培酮并未增强大鼠的探索性活动。联合使用氟西汀或米氮平与利培酮并未降低 FST 中应激引起的血浆皮质酮浓度升高。
研究结果表明，低剂量利培酮增强了氟西汀和米氮平在 FST 中的抗抑郁样作用（但不能使这些大鼠的应激诱导的皮质酮水平升高正常化），5-HT1A 受体可能在这些作用中发挥一定作用。
