Peripherally administered benzodiazepines increase morphine-induced analgesia in the rat. Effect of RO 15-3505 and FG 7142.

The influence of alprazolam, chlordiazepoxide and midazolam on the antinociceptive effect of subcutaneous morphine was investigated in rats, using the tail-flick test. After intraperitoneal administration, all drugs significantly enhanced the morphine-induced analgesia. Both the benzodiazepine receptor antagonist RO 15-3505 and the benzodiazepine receptor inverse agonist FG 7142 antagonized the potentiating effect of alprazolam, chlordiazepoxide and midazolam. Our results suggest that the interaction between benzodiazepines and opioids in modulating nociceptive responses involves primarily benzodiazepine receptors and that different pathways are involved in the anxiolytic and pro-analgesic actions of benzodiazepines.