Benzodiazepines and their antagonists interfere with opioid-dependent stress-induced analgesia.

Timing or intensity of shocks significantly modify the characteristics of the analgesia induced by footshock, and conditioning to footshock induces analgesia, independently from the time and shock parameters used for conditioning. However, whatever the parameters of shock, and the presence of conditioning or not, the stress has to be inescapable in order to produce an increase in pain thresholds. This observation suggests that anxiety plays a major role in the development of stress-induced analgesia. In order to test this hypothesis we investigated the effects of the benzodiazepine agonists diazepam and clonazepam, the antagonists RO 15-1788, CGS 8216, CGS 9896, and the inverse agonists FG 7142 and FG 7041 on the development and maintenance of stress-induced analgesia. Benzodiazepine receptor agonists decreased the analgesic effect of inescapable footshock, benzodiazepine receptor antagonists increased the footshock induced analgesia, whereas inverse agonists did not modify the analgesia induced by the shock. All the benzodiazepine receptor ligands blocked the antagonism of the footshock analgesia induced by naloxone.