Dissociation of the opioid and nonopioid effects of cyclazocine

Lower IV doses of (dl)- and (l)-cyclazocine (0.05 and 0.50 mg/kg) in the rat produced opioid EEG and behavioral effects that were antagonized by naltrexone pretreatment. Higher IV doses of (dl)- and (l)-cyclazocine (1.00 and 2.00 mg/kg) produced initial "psychotomimetic-like" behavioral effects that were naltrexone-resistant, followed by the delayed emergence of opioid EEG and behavioral effects that were naltrexone-sensitive, (d)-Cyclazocine produced only "psychotomimetic-like" behavioral effects that were naltrexone-resistant. (dl)-Cyclazocine antagonized morphine-induced EEG and behavioral effects in naive rats. (l)-Cyclazocine precipitated withdrawal symptoms in morphine-dependent rats. In contrast, (d)-cyclazocine produced "psychotomimetic-like" effects, but no withdrawal symptoms. Thus, (dl)- and (l)-cyclazocine produced dose- and time-related opioid and nonopioid "psychotomimetic-like" effects, while (d)-cyclazocine produced only nonopioid "psychotomimetic-like" effects.