Hill Matthew N, Kambo Jaspreet S, Sun Jane C, Gorzalka Boris B, Galea Liisa A M
Department of Psychology and the Brain Research Centre, University of British Columbia, Vancouver, BC, Canada V6T1Z4.
Eur J Neurosci. 2006 Oct;24(7):1845-9. doi: 10.1111/j.1460-9568.2006.05061.x.
The endocannabinoid system has been shown to regulate both the hypothalamic-pituitary-adrenal (HPA) axis and emotionality. The present experiment was designed to examine whether pharmacological modulation of the endocannabinoid system would affect the suppression of hippocampal cell proliferation and increase in defensive behaviours seen following exposure to predator odour (trimethylthiazoline; TMT) stress. Rats were administered either an endocannabinoid uptake inhibitor (AM404; 2 mg/kg) or a cannabinoid CB1 receptor antagonist (AM251; 5 mg/kg) 30 min prior to exposure to TMT. Exposure to TMT reduced cell proliferation in the dentate gyrus and increased the expression of defensive burying. Administration of AM404 significantly inhibited defensive burying, and attenuated the reduction in cell proliferation in response to TMT exposure. Administration of AM251 alone significantly increased cell proliferation; however, pretreatment with AM251 prevented neither the stress-induced suppression of cell proliferation nor the stress-induced increase in behavioural responses. These results support previous research demonstrating that augmentation of endocannabinoid signalling can suppress stress-responsive systems. They also suggest that endocannabinoids may play a complex role in the regulation of neurogenesis via cell proliferation in the hippocampus.
内源性大麻素系统已被证明可调节下丘脑 - 垂体 - 肾上腺（HPA）轴和情绪。本实验旨在研究对内源性大麻素系统进行药理学调节是否会影响暴露于捕食者气味（三甲基噻唑啉；TMT）应激后所观察到的海马细胞增殖抑制和防御行为增加。在暴露于TMT前30分钟，给大鼠施用内源性大麻素摄取抑制剂（AM404；2毫克/千克）或大麻素CB1受体拮抗剂（AM251；5毫克/千克）。暴露于TMT会减少齿状回中的细胞增殖，并增加防御性埋藏行为的表达。施用AM404可显著抑制防御性埋藏行为，并减弱因暴露于TMT而导致的细胞增殖减少。单独施用AM251可显著增加细胞增殖；然而，用AM251预处理既不能防止应激诱导的细胞增殖抑制，也不能防止应激诱导的行为反应增加。这些结果支持了先前的研究，即内源性大麻素信号增强可抑制应激反应系统。它们还表明，内源性大麻素可能在通过海马细胞增殖调节神经发生中发挥复杂作用。
