Antidepressant-like effects of kappa-opioid receptor antagonists in Wistar Kyoto rats.
Antidepressant-like effects of kappa-opioid receptor antagonists in Wistar Kyoto rats.
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DOI：
10.1038/npp.2009.183
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发表时间：
2010-02
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影响因子：
--
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中科院分区：
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--
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The Wistar Kyoto (WKY) rat strain is a putative genetic model of comorbid depression and anxiety. Previous research showing increased kappa opioid receptor (KOR) gene expression in the brains of WKY rats, combined with studies implicating the KOR in animal models of depression and anxiety, suggest that alterations in the KOR system could play a role in the WKY behavioral phenotype. Here, the effects of KOR antagonists in the forced swim test (FST) were compared in the WKY and the Sprague Dawley (SD) rat strains. As previously reported, WKY rats displayed more immobility behavior than SD rats. The KOR antagonists selectively produced antidepressant-like effects in the WKY rats. By contrast, the antidepressant desipramine reduced immobility in both strains. Brain regions potentially underlying the strain-specific effects of KOR antagonists in the FST were identified using c-fos expression as a marker of neuronal activity. The KOR antagonist nor-binaltorphimine produced differential effects on the number of c-fos positive profiles in the piriform cortex and nucleus accumbens shell between SD and WKY rats. The piriform cortex and nucleus accumbens also contained higher levels of KOR protein and dynorphin A peptide, respectively, in the WKY strain. In addition, local administration of nor-BNI directly into the piriform cortex produced antidepressant-like effects in WKY rats further implicating this region in the antidepressant-like response to KOR antagonists. These results support the use of the WKY rat as a model of affective disorders potentially involving KOR overactivity and provide more evidence that KOR antagonists could potentially be utilized as novel antidepressants.
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