Nitric oxide synthase inhibitors augment the effects of serotonin re-uptake inhibitors in the forced swimming test

被引:0
作者
Harkin, A [1 ]
Connor, TJ [1 ]
Burns, MP [1 ]
Kelly, JP [1 ]
机构
[1] Natl Univ Ireland Univ Coll Galway, Dept Pharmacol, Galway, Ireland
关键词
nitric oxide synthase; N-G-nitro-L-arginine; 7-nitroindazole; selective serotonin re-uptake inhibitor; antidepressant; forced swimming test;
D O I
暂无
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The problem of antidepressant-resistant depression has necessitated finding ways of augmenting the actions of currently existing antidepressants. The present studies investigate the possibility of synergistic interactions between nitric oxide (NO) synthase inhibitors and antidepressants in the mouse forced swim test (FST), a pre-clinical test of antidepressant activity. Treatment with a behaviourally subactive dose of the NO synthase inhibitor N-G-nitro-L-arginine (L-NA) (3 mg/kg) augmented the behavioural effect of the tricyclic antidepressant imipramine. In a similar fashion L-NA (3 mg/kg) augmented the effect of the selective serotonin re-uptake inhibitor (SSRI) fluoxetine but not the noradrenaline re-uptake inhibitor, reboxetine in the FST. The interaction observed between L-NA and fluoxetine generalised to other selective serotonin re-uptake inhibitors, namely, sertraline and citalopram in the FST. Treatment with a subactive dose of the neuronally selective NO synthase inhibitor, 7-nitroindazole (30 and 50 mg/kg), augmented the behavioural effects of imipramine and fluoxetine, respectively. Thus inhibition of NO synthase enhances the activity of antidepressants that work via a serotonergic mechanism in the FST. The results of the present investigation support a view that antidepressant effects, or enhancement of such effects in the FST, may be elicited via NO synthase inhibition. Furthermore, these data raise the possibility that inhibition of NO synthase could be used as a strategy to enhance the clinical efficacy of serotonergic antidepressants. (C) 2003 Elsevier B.V/ECNP. All rights reserved.
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页码:274 / 281
页数:8
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