Teal J J, Holtzman S G
Pharmacol Biochem Behav. 1980 Apr;12(4):587-93. doi: 10.1016/0091-3057(80)90193-8.
The ability of narcotic antagonists to block the discriminative stimulus effects of 3.0 mg/kg (IM) of morphine was evaluated quantitatively in the squirrel monkey using a two-choice discrete-trial avoidance paradigm. The time-course and relative potency of naloxone and naltrexone for antagonizing morphine's stimulus effects in the squirrel monkey was similar to those determined in rats and pigeons. Complete blockade of morphine's effects was attained with 0.03 mg/kg of either antagonist when given simultaneously with morphine, but only naltrexone completely blocked the stimulus effects of morphine when the pretreatment interval was extended to 12 and 18 hr. A Schild plot derived from the degree of antagonism of graded doses of morphine by graded doses of naltrexone (0.003-0.1 mg/kg) yielded a line with a slope of -0.63 +/- 0.2 and an apparent pA2 value of 8.25 +/- 0.2. These results demonstrate the feasibility of quantitatively assessing the drug-receptor interactions that subserve the discriminative stimulus effects of morphine in the squirrel monkey.
使用双选择离散试验回避范式，在松鼠猴中定量评估了麻醉拮抗剂阻断3.0毫克/千克（肌肉注射）吗啡的辨别刺激效应的能力。纳洛酮和纳曲酮在松鼠猴中拮抗吗啡刺激效应的时间进程和相对效力与在大鼠和鸽子中确定的相似。当与吗啡同时给予时，0.03毫克/千克的任何一种拮抗剂都能完全阻断吗啡的效应，但只有纳曲酮在预处理间隔延长至12小时和18小时时能完全阻断吗啡的刺激效应。由纳曲酮（0.003 - 0.1毫克/千克）分级剂量对吗啡分级剂量的拮抗程度得出的Schild图产生了一条斜率为-0.63±0.2且表观pA2值为8.25±0.2的线。这些结果证明了定量评估药物-受体相互作用的可行性，这些相互作用有助于吗啡在松鼠猴中的辨别刺激效应。
