期刊
BIOLOGICAL PSYCHIATRY
卷 70, 期 5, 页码 479-486出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2011.04.022
关键词
Anxiety; cannabinoid receptor 2 (CB2); endocannabinoid; memory; nociception; tolerance
资金
- Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) [CB06/03]
- Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III (FIS/ISCIII) [PI081913]
- Spanish Ministry of Science and Innovation [SAF2009-07309, SAF2007-64062]
- PLAN E (Plan Espanol para el Estimulo de la Economia y el Empleo)
- La Marato de TV3 2009 [090910]
- European Commission [LSHM-CT-2004-05166, LSHM-CT-2007-037669]
- Generalitat de Catalunya [2005SGR00131]
- ICREA (Institucio Catalana de Recerca i Estudis Avancats)
- Spanish Ministry of Education and Culture
Background: Cannabinoid agonists are potential therapeutic agents because of their antinociceptive and anxiolytic-like effects, although an important caveat to their use is the possible adverse responses related to memory impairment. An alternative approach to circumvent this limitation consists of enhancing the concentration of the endocannabinoids anandamide and 2-arachidonoylglycerol. Methods: Using low doses of the specific inhibitors of the endocannabinoid metabolizing enzymes fatty acid amide hydrolase, URB597, and monoacylglycerol lipase, JZL184, we analyzed their acute and chronic effects on memory consolidation, anxiolytic-like effects, and nociception in mice (n = 6-12 per experimental group). Results: We show that anandamide is a central component in the modulation of memory consolidation, whereas 2-arachidonoylglycerol is not involved in this process. Interestingly, both URB597 and JZL184 induce anxiolytic-like effects through different cannabinoid receptors. In addition, the results show that the antinociceptive and anxiolytic-like responses of both inhibitors, as well as their acute effects on memory consolidation, are maintained after chronic treatment. Conclusions: These results dissociate the role of anandamide and 2-arachidonoylglycerol in memory consolidation and anxiety and reveal the interest of cannabinoid receptor 2 as a novel target for the treatment of anxiety-related disorders.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据