Reversal of Antinociceptive Effect of Cholecystokinin by Benzodiazepines and a Benzodiazepine Antagonist, Ro 15-1788

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Abstract
I.p. administered benzodiazepines, chlordiazepoxide (2-5 mg/kg), diazepam (1 mg/kg), flurazepam (1 mg/kg) and a benzodiazepine antagonist, Ro 15-1788 [flumazepil] (0.5 mg/kg), reversed the antinociceptive effect in mice which was induced by intracisternal administration of 1 .mu.g of sulfated cholecystokinin octapeptide. The antinociceptive effect of echolecystokinin was reversed by naloxone, suggesting that the antinociceptive action involved endogenous opioid peptides in its production. Morphine-induced analgesia was not reversed by diazepam and Ro 15-1788. These facts rule out opioid receptors as the site of the antagonism between the benzodiazepines or Ro 15-1788 and cholecystokinin on the antinociceptive effect. Benzodiazepines and Ro 15-1788 seem to inhibit the release of opioid peptides induced cholecystokinin.