Naloxone-precipitated withdrawal as a function of the morphine-naloxone interval

Withdrawal was precipitated by naloxone at different intervals, up to 22.5 h, following a last maintenance injection in morphine-dependent rats. Different symptoms of withdrawal were found to be preeminent following different morphine-naloxone intervals. Locomotor activity, jumping, and writhing were precipitated most frequently at shorter intervals after the last morphine injection; teeth chattering, wet dog shakes, ptosis, diarrhea, penile ejaculation, and hypothermia, at longer intervals. Others, including hostility, rhinnorhea and lacrimation did not change in frequency over the intervals measured. This order closely resembled that in which symptoms occurred as a result of withdrawal abstinence alone, though they were somewhat advanced in time. The results were discussed in relation to previously reported observations of naloxone-precipitated withdrawal, and in terms of their implications for a general theory of morphine withdrawal.