Fride E
Department of Natural Products, Hebrew University Medical Faculty, Jarusalem, Israel.
Brain Res. 1995 Oct 30;697(1-2):83-90. doi: 10.1016/0006-8993(95)00790-w.
In this study we examined whether tolerance develops to chronic exposure to anandamides [20:4, n-6 (ANA) and 20:3, n-6 (HLEA)] two of the recently discovered endogenous cannabinoid receptor ligands in brain. Tolerance to ANA and cross-tolerance to delta 9-tetrahydrocannabinol (delta 9-THC) was examined in female Sabra or C57BL/6 mice which had received daily injections (i.p.) of low (0.001-1 mg/kg) or high doses (20 mg/kg) of ANA or HLEA for 2 weeks. Twenty four h after the last injection, the mice were challenged with 20 mg/kg ANA or delta 9-THC. Animals were subjected to a series of tests frequently used to assess cannabinoid-induced effects. The results indicated that the high dose, but not the low doses of anandamides produced tolerance to ANA and cross-tolerance to delta 9-THC for motor activity in an open field, catalepsy on a ring, hypothermia and analgesia on a hot plate. One week after the last ANA treatment, tolerance was not present anymore. No tolerance to ANA was observed for reduced defecation in the open field, a measure of intestinal hypomotility. This phenomenon may possibly be attributed to a difference between activities produced through different types of cannabinoid receptors.
在本研究中，我们检测了对脑中最近发现的两种内源性大麻素受体配体——花生四烯乙醇胺[20:4, n-6 (ANA)和20:3, n-6 (HLEA)]的慢性暴露是否会产生耐受性。在雌性Sabra或C57BL/6小鼠中检测了对ANA的耐受性以及对δ9-四氢大麻酚（δ9-THC）的交叉耐受性，这些小鼠每天腹腔注射低剂量（0.001 - 1 mg/kg）或高剂量（20 mg/kg）的ANA或HLEA，持续2周。在最后一次注射后24小时，用20 mg/kg的ANA或δ9-THC对小鼠进行激发试验。对动物进行了一系列常用于评估大麻素诱导效应的测试。结果表明，高剂量而非低剂量的花生四烯乙醇胺会使小鼠对ANA产生耐受性，并对旷场中的运动活动、环上的僵住症、体温过低以及热板上的镇痛作用对δ9-THC产生交叉耐受性。在最后一次ANA处理一周后，耐受性不再存在。在旷场中排便减少（一种肠道运动减弱的指标）方面，未观察到对ANA的耐受性。这种现象可能归因于通过不同类型大麻素受体产生的活动之间的差异。
