Diazepam-induced release of opioid activity in the rat brain.

Acute intravenous injection of diazepam (2.5 mg/kg) in rats resulted in a moderate (2-fold) increase in pain threshold, as measured by the 'vocalization test'. This effect was not antagonized by naloxone (10 mg/kg, i.p.). However, pretreatment of the animals with the enzyme-inhibitor, bacitracin (50 micrograms, i.c.v.), dramatically enhanced the diazepam-induced antinociception. This increased effect was partially antagonized by naloxone, indicating an opioid-mediated mechanism as involved and further supports the hypothesis that benzodiazepine application may release opioid peptides in restricted areas of the CNS.