The current study examined the conditions that are necessary and sufficient for the initiation and progression of acute
morphine dependence using two indices of
opiate withdrawal: suppression of operant response rates and a somatic withdrawal rating scale. Separate groups of rats were pretreated with
morphine (5 mg/kg, s.c.) a total of three times at intervals of 24 h, 1, 3, or 6 weeks. Rats received a single dose of
naloxone 4 h after each
morphine pretreatment.
Naloxone-induced suppression of operant responding (0.33 mg/kg, s.c.) was significantly potentiated with repeated exposure to
morphine even at the 6-week inter-treatment interval (ITI). At 24-h, 1-week and 3-week ITIs, rats treated with
naloxone only after the third and final
morphine pretreatment showed similar suppression of operant responding following
naloxone to rats treated with
naloxone after all three
morphine pretreatments. However, at the 6-week ITI, the response-disruptive effects of
naloxone administered for the first time after the third
morphine pretreatment were no greater than the effects of
naloxone administered after a single
morphine pretreatment. In contrast to results seen with suppression of operant responding as the withdrawal index, potentiation of somatic signs of withdrawal was observed only at the 24-h ITI. These results indicate that a neuroadaptive state resembling
opiate dependence can be initiated after just one injection of
morphine, and that the response-disruptive effects of
naloxone appear to be a particularly sensitive index of the initiation and progression of acute
opiate dependence.