Tepper P, Woods J H
Psychopharmacology (Berl). 1978 Jul 6;58(2):125-9. doi: 10.1007/BF00426894.
Acute i.p. administration of morphine or cocaine produced increase in locomotor activity in Swiss-Webster female mice that were maximal at 32-100 mg/kg for morphine and at 32 mg/kg for cocaine. WIN 35, 197-2 produced dose-dependent decreases in locomotor activity from 3.2-32 mg/kg. Chronic administration of WIN 35, 197-2 led to a 6-10 fold shift to the right in the locomotor activity decreasing effect of the drug, but WIN 35, 197-2-tolerant mice retained their sensitivity to the locomotor stimulant effects of morphine and cocaine. Acute administration of WIN 35, 197-2 failed to sensitize mice to naloxone-induced jumping, although morphine did so. Chronic administration of WIN 35, 197-2 did lead to sensitization to naloxone, but WIN 35, 197-2 was much less efficacious in this regard than morphine. These behavioral effects of WIN 35, 197-2 may be helpful in the classification of modes of action of different narcotic agonists.
对瑞士-韦伯斯特雌性小鼠腹腔注射吗啡或可卡因后，可使其运动活性增加，吗啡的最大有效剂量为32 - 100毫克/千克，可卡因为32毫克/千克。WIN 35,197 - 2在3.2 - 32毫克/千克剂量范围内可使运动活性呈剂量依赖性降低。长期给予WIN 35,197 - 2可使该药物降低运动活性的作用向右偏移6 - 10倍，但对WIN 35,197 - 2产生耐受的小鼠对吗啡和可卡因的运动兴奋作用仍保持敏感。急性给予WIN 35,197 - 2未能使小鼠对纳洛酮诱导的跳跃产生敏感化，而吗啡则可以。长期给予WIN 35,197 - 2确实会导致对纳洛酮的敏感化，但在这方面WIN 35,197 - 2的效果远不如吗啡。WIN 35,197 - 2的这些行为效应可能有助于对不同麻醉激动剂的作用模式进行分类。
