Lamb R J, Järbe T U, Makriyannis A, Lin S, Goutopoulos A
Departments of Psychiatry and Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Eur J Pharmacol. 2000 Jun 16;398(2):251-8. doi: 10.1016/s0014-2999(00)00318-6.
We examined the effects of Delta 9-tetrahydrocannabinol (Delta 9-THC), (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide ((R)-methanandamide, AM 356), SR 141716, and d-amphetamine on fixed-ratio (FR) responding maintained by food in rats before and during daily dosing with Delta 9-THC. Rats responded under a FR 10 schedule of food reinforcement. Cumulative dose-response curves for the various drugs were determined before and during daily Delta 9-THC administration. All four drugs dose-dependently decreased responding both before and during daily dosing with Delta 9-THC (18 mg/kg/day). The dose-response curves for both Delta 9-THC and (R)-methanandamide were shifted to the right with daily dosing with Delta 9-THC, indicating tolerance to the effects of Delta 9-THC and cross-tolerance to the effects of (R)-methanandamide. The doses of d-amphetamine examined produced similar effects both before and during daily dosing with Delta 9-THC. The effects of SR 141716 were not consistently altered by daily Delta 9-THC administration. These results indicate that tolerance develops to the effects of Delta 9-THC, when Delta 9-THC is administered repeatedly. These results also indicate that cross-tolerance to (R)-methanandamide develops with repeated Delta 9-THC administration.
我们研究了9-四氢大麻酚（Delta 9-THC）、（R）-（+）-花生四烯酰-1'-羟基-2'-丙酰胺（（R）-甲磺酰胺，AM 356）、SR 141716和右旋苯丙胺对大鼠在每日给予Delta 9-THC之前和期间由食物维持的固定比率（FR）反应的影响。大鼠在FR 10食物强化程序下做出反应。在每日给予Delta 9-THC之前和期间测定了各种药物的累积剂量-反应曲线。在每日给予Delta 9-THC（18 mg/kg/天）之前和期间，所有四种药物均剂量依赖性地降低反应。随着每日给予Delta 9-THC，Delta 9-THC和（R）-甲磺酰胺的剂量-反应曲线均向右移动，表明对Delta 9-THC的作用产生耐受性，并对（R）-甲磺酰胺的作用产生交叉耐受性。在每日给予Delta 9-THC之前和期间，所检测的右旋苯丙胺剂量产生相似的效果。每日给予Delta 9-THC并未始终改变SR 141716的效果。这些结果表明，当反复给予Delta 9-THC时，会对其作用产生耐受性。这些结果还表明，反复给予Delta 9-THC会对（R）-甲磺酰胺产生交叉耐受性。
