Comparative study in mice of flunitrazepam vs. diazepam on morphine withdrawal syndrome

1. There is some evidence that benzodiazepine may modify the opioid withdrawal syndrome. We have investigated the effect of two different benzodiazepines, diazepam and flunitrazepam, on the morphine withdrawal syndrome experimentally induced in mice. 2. Opiate dependence has been induced by administration of morphine s.c. over a period of five days. Two hours after last morphine administration withdrawal syndrome was induced by s.c. injection of naloxone (5mg/kg). The number of jumps, wet-dog-shakes and paw tremor, and the presence or absence of ptosis, diarrhea, teeth chattering and body tremor were evaluated after naloxone injection. 3. All the signs of morphine withdrawal syndrome was antagonized by flunitrazepam and diazepam, only wet-dog-shake was strongly increased by flunitrazepam.