RAPID INDUCTION OF CONDITIONED OPIATE WITHDRAWAL IN THE RAT

Previous studies of conditioned opiate withdrawal in animals either have suffered from a lack of readily quantifiable data (e.g., measurement of diarrhea and vocalization in rodents) or were very long and costly (e.g., disruption of operant responding in monkeys). In this study, an attempt was made to produce a rapid and quantifiable measure of conditioned opiate withdrawal in the mt. Rats were trained to lever-press for food reinforcement on a fixed-ratio-15 schedule. All rats were then implanted with two subcutaneous 75-mg morphine pellets and allocated into three groups. The paired group received four naloxone injections (0.025 mg/kg SC) in the operant chambers paired with a distinctive tone and smell. The unpaired group was also exposed to the tone and smell in the chambers on four occasions, but received the naloxone injections in the home cage. The saline control animals were never exposed to naloxone or the tone and smell. On the test day, all rats were exposed to the tone and smell and injected with saline. The paired group showed a significant reduction in operant responding in response to the tone and smell when compared either with the other two groups, or to their own response rates on the previous day. In a second experiment, the paired and unpaired groups were again challenged with the tone and smell and a saline injection 1 month after removal of the morphine pellets. Again, the paired group showed a significant disruption of response. These results suggest that the conditioned stimulus acquired significant behavior-disruptive properties manifest even in the absence of opiate receptor occupancy. A rapidly acquired, quantifiable measure of conditioned withdrawal in the rat will allow systematic evaluation of the neurobiological basis for this phenomenon.