Schedule-controlled behavior in the morphine-dependent and post-dependent rat.

Chronic morphine treatment has been reported to induce long-lasting changes in the responses of animals to the subsequent administration of morphine or narcotic antagonists. However, there have been few systematic studies in which the effects of morphine or narcotic antagonists have been compared in the same group of animals before, during, and after chronic morphine administration. Rats were trained to press a lever on a variable interval (1 min) schedule of food presentation and dose-response curves were determined for morphine (0.3--30 mg/kg) and naloxone (0.003--10 mg/kg) in the same group of animals prior to, during, and following morphine dependence. Dependence was induced and maintained by scheduled access to 0.05% morphine drinking solution for 10 min every 6 h. Response rates and fluid intake remained constant over the 9 month study. The dose-response curves for morphine and naloxone in predependent and dependent animals were similar to those previously reported in studies using other schedules of reinforcement and different techniques for establishing morphine dependence: chronic morphine treatment produced a threefold decrease in the effect of morphine and a dramatic increase in the effectiveness of naloxone in decreasing response rate. The altered sensitivity of dependent rats to morphine and naloxone was completely reversed in the post-dependent animals, within 4 weeks after the withdrawal of morphine. Scheduled access to a morphine solution affords a simple means of maintaining morphine-tolerant and dependent animals for long-term behavioral studies.