Differential protracted effects of morphine and ethylketocyclazocine challenges on EEG and behavior in the rat

One group of six adult female Sprague-Dawley rats was given a series of automatically administered i.v. morphine injections over eight days. Similarly, a second group of six rats was given ethylketocyclazocine (EKC). Control rats received chronic i.v. saline injections. Tolerance to EEG and behavioral effects of morphine and EKC was demonstrated. At 15 days morphine post-withdrawal, morphine challenges produced EEG and behavioral stupor for a mean of 5 min, followed by EEG and behavioral arousal for a mean of 131 min. In contrast, morphine challenges in saline control rats produced a biphasic EEG and behavioral response consisting of a mean of 85 min of stupor, followed by a mean of 88 min of arousal. However, at 15 days EKC post-withdrawal, EKC challenges produced a biphasic EEG and behavioral response consisting of a mean of 57 min of depression followed by a mean of 55 min of arousal; control saline rats demonstrated similar responses to EKC challenges. Similar results were obtained at one month post-withdrawal for all groups. Thus, protracted effects on EEG and behavior were evident in rats chronically treated with morphine, but not in rats chronically treated with EKC.