Moise Anna M, Eisenstein Sarah A, Astarita Giuseppe, Piomelli Daniele, Hohmann Andrea G
Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA 30602-3013, USA.
Psychopharmacology (Berl). 2008 Oct;200(3):333-46. doi: 10.1007/s00213-008-1209-5. Epub 2008 Jun 11.
An endocannabinoid signaling system has not been identified in hamsters.
We examined the existence of an endocannabinoid signaling system in Syrian hamsters using neuroanatomical, biochemical, and behavioral pharmacological approaches.
The distribution of cannabinoid receptors was mapped, and membrane fatty-acid amide hydrolase (FAAH) activity and levels of fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test, and models of unconditioned and conditioned social defeat.
A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain using [3H]CP55,940 binding and autoradiography. The FAAH inhibitor URB597 inhibited FAAH activity (IC50 = 12.8 nM) and elevated levels of fatty-acid amides (N-palmitoyl ethanolamine and N-oleoyl ethanolamine) in hamster brain. Anandamide levels were not reliably altered. The cannabinoid agonist WIN55,212-2 (1- 10 mg/kg i.p.) induced CB1-mediated motor ataxia. Blockade of CB1 with rimonabant (5 mg/kg i.p.) induced anxiogenic-like behavior in the elevated plus maze. URB597 (0.1-0.3 mg/kg i.p.) induced CB1-mediated anxiolytic-like effects in the elevated plus maze, similar to the benzodiazepine diazepam (2 mg/kg i.p.). Diazepam (2-6 mg/kg i.p.) suppressed the expression, but not the acquisition, of conditioned defeat. By contrast, neither URB597 (0.3-3.0 mg/kg i.p.) nor rimonabant (5 mg/kg i.p.) altered unconditioned or conditioned social defeat or rota-rod performance.
Endocannabinoids engage functional CB1 receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Our results further suggest that neither unconditioned nor conditioned social defeat in the Syrian hamster is dependent upon cannabinoid CB1 receptor activation.
尚未在仓鼠中鉴定出内源性大麻素信号系统。
我们使用神经解剖学、生物化学和行为药理学方法研究叙利亚仓鼠体内内源性大麻素信号系统的存在情况。
绘制大麻素受体的分布图，并测量仓鼠脑中膜脂肪酸酰胺水解酶（FAAH）的活性以及脂肪酸酰胺水平。在高架十字迷宫、转棒试验以及无条件和条件性社会挫败模型中评估大麻素CB1受体阻断和FAAH抑制的影响。
使用[3H]CP55,940结合和放射自显影技术在仓鼠脑中检测到大麻素受体具有特征性的异质性分布。FAAH抑制剂URB597抑制了仓鼠脑中的FAAH活性（IC50 = 12.8 nM）并提高了脂肪酸酰胺（N-棕榈酰乙醇胺和N-油酰乙醇胺）的水平。花生四烯乙醇胺水平未发生可靠改变。大麻素激动剂WIN55,212-2（1 - 10 mg/kg腹腔注射）诱导CB1介导的运动性共济失调。用利莫那班（5 mg/kg腹腔注射）阻断CB1在高架十字迷宫中诱导出焦虑样行为。URB597（0.1 - 0.3 mg/kg腹腔注射）在高架十字迷宫中诱导出CB1介导的抗焦虑样效应，类似于苯二氮䓬类药物地西泮（2 mg/kg腹腔注射）。地西泮（2 - 6 mg/kg腹腔注射）抑制条件性挫败的表达，但不影响其获得。相比之下，URB597（0.3 - 3.0 mg/kg腹腔注射）和利莫那班（5 mg/kg腹腔注射）均未改变无条件或条件性社会挫败或转棒试验表现。
内源性大麻素作用于仓鼠脑中具有功能的CB1受体以抑制焦虑样行为，并经历由FAAH催化的酶促水解。我们的结果进一步表明，叙利亚仓鼠的无条件或条件性社会挫败均不依赖于大麻素CB1受体激活。
