Magour S, Coper H, Fähndrich C
Psychopharmacology (Berl). 1977 Jan 31;51(2):141-5. doi: 10.1007/BF00431730.
Rats were injected intraperitoneally once every 12 h with 10 mg/kg delta-9-THC and the time course of the depressant effect was determined after one and nine injections. The motor activity of naive rats was maximally depressed between 1 and 4 h and returned to control levels 8 h after treatment. After nine injections, the maximum intensity of the depressant effect was not different from that after one injection but had completely disappeared at an earlier time point (4 h p.i.) indicating the development of tolerance to the duration of effect on motor activity. The subcellular distribution studies in brains of tolerant and non-tolerant rats indicated that an accelerated shift in the concentrations of delta-9-THC and 11-OH-delta-9-THC towards highly polar metabolites in the brains, rather than an increased elimination of these cannabinoids or decreased sensitivity of the brain may be responsible for the development of tolerance to delta-9-THC.
大鼠每12小时腹腔注射一次10毫克/千克的Δ⁹-四氢大麻酚，在注射一次和九次后测定其抑制作用的时间进程。未经处理的大鼠的运动活性在1至4小时之间受到最大程度的抑制，并在治疗后8小时恢复到对照水平。九次注射后，抑制作用的最大强度与注射一次后没有差异，但在更早的时间点（注射后4小时）就完全消失了，这表明对运动活性作用持续时间产生了耐受性。对耐受和未耐受大鼠大脑的亚细胞分布研究表明，大脑中Δ⁹-四氢大麻酚和11-羟基-Δ⁹-四氢大麻酚浓度加速向高极性代谢物转变，而非这些大麻素的消除增加或大脑敏感性降低，可能是对Δ⁹-四氢大麻酚产生耐受性的原因。
