期刊
NEUROPSYCHOPHARMACOLOGY
卷 36, 期 6, 页码 1275-1288出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2011.13
关键词
mood; anxiety; 5-HT receptors; antidepressant; dorsal raphe; neurogenesis
资金
- University Claude Bernard Lyon 1
- CNRS
- Astra Zeneca
- Bristol Myers Squibb
- Janssen
- Pfizer
- Merck Squibb
- Merck
- Labopharm
- Servier
- Eli Lilly
- Lundbeck
- Solvay
Current antidepressants still display unsatisfactory efficacy and a delayed onset of therapeutic action. Here we show that the pharmacological blockade of serotonin 7 (5-HT7) receptors produced a faster antidepressant-like response than the commonly prescribed antidepressant fluoxetine. In the rat, the selective 5-HT7 receptor antagonist SB-269970 counteracted the anxiogenic-like effect of fluoxetine in the open field and exerted an antidepressant-like effect in the forced swim test. In vivo, 5-HT7 receptors negatively regulate the firing activity of dorsal raphe 5-HT neurons and become desensitized after long-term administration of fluoxetine. In contrast with fluoxetine, a 1-week treatment with SB-269970 did not alter 5-HT firing activity but desensitized cell body 5-HT autoreceptors, enhanced the hippocampal cell proliferation, and counteracted the depressive-like behavior in olfactory bulbectomized rats. Finally, unlike fluoxetine, early-life administration of SB-269970, did not induce anxious/depressive-like behaviors in adulthood. Together, these findings indicate that the 5-HT7 receptor antagonists may represent a new class of antidepressants with faster therapeutic action. Neuropsychopharmacology (2011) 36, 1275-1288; doi: 10.1038/npp.2011.13; published online 16 February 2011
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