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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.

Changes in locomotor activity and naloxone-induced jumping in mice produced by WIN 35,197-2 (Ethylketazocine) and morphine