Downs D A, Woods J H
J Pharmacol Exp Ther. 1976 Feb;196(2):298-306.
The effects of morphine, pentazocine, naloxone and combinations of these drugs on schedule-controlled behavior were examined in rhesus monkeys and pigeons. The order of potency in decreasing response rates under a multiple 5-minute fixed-interval, 30-response fixed-ratio schedule in both monkeys and pigeons was morphine greater than pentazocine greater than naloxone. Compared to monkeys, pigeons were less sensitive to morphine and pentazocine and slightly more sensitive to naloxone. In monkeys and pigeons, as the morphine dose increased, higher naloxone doses were required to restore responding to or near control levels. In pigeons, however, the response rate decreases caused by naloxone prevented the complete antagonism of the highest morphine dose and limited the range of naloxone doses over which complete antagonism of morphine occurred. Antagonism of pentazocine by naloxone generally was greatest at the lowest pentazocine dose tested in both monkeys and pigeons. At higher pentazocine doses, if any antagonism was obtained, it was slight, and the amount of antagonism typically did not increase as the naloxone dose increased. Pentazocine generally failed to antagonize morphine in monkeys and pigeons.
在恒河猴和鸽子身上研究了吗啡、喷他佐辛、纳洛酮以及这些药物组合对按程序控制行为的影响。在猴子和鸽子中,按照5分钟固定间隔、30次反应固定比率的复合时间表,降低反应率的效力顺序为吗啡大于喷他佐辛大于纳洛酮。与猴子相比,鸽子对吗啡和喷他佐辛的敏感性较低,对纳洛酮的敏感性略高。在猴子和鸽子中,随着吗啡剂量增加,需要更高的纳洛酮剂量才能使反应恢复到或接近对照水平。然而,在鸽子中,纳洛酮引起的反应率降低阻止了对最高吗啡剂量的完全拮抗,并限制了发生吗啡完全拮抗的纳洛酮剂量范围。在猴子和鸽子中,在测试的最低喷他佐辛剂量下,纳洛酮对喷他佐辛的拮抗作用通常最大。在较高的喷他佐辛剂量下,如果有任何拮抗作用,也是轻微的,并且拮抗作用的程度通常不会随着纳洛酮剂量的增加而增加。喷他佐辛在猴子和鸽子中通常不能拮抗吗啡。