Are the analgesic effects of social defeat mediated by benzodiazepine receptors?

Social conflict in mice is associated with at least two forms of analgesia. A long-lasting opioid reaction is evident in intruder mice exposed to prolonged attack, whilst an acute non-opioid analgesia is seen in response to either defeat experience per se or the territorial scent-marking of an aggressive conspecific. Recent work from this laboratory has suggested that the non-opioid analgesic reaction to defeat experience may be mediated via benzodiazepine receptor mechanisms. The present studies were designed to further test this tentative hypothesis. Results confirmed that defeat analgesia is dose-dependently blocked by Ro15-1788 (20-40 mg/kg) and diazepam (2-4 mg/kg), and also indicated partial antagonism of the reaction by CGS8216 (2.5 mg/kg). The partial agonists CGS9896 (2.5-20 mg/kg) and ZK91296 (2.5-20 mg/kg) were ineffective in blocking the reaction, a finding also obtained with the full agonist ZK93423 (0.05-10 mg/kg). However, the antagonist/weak inverse agonist ZK93426 was found to possess significant intrinsic analgesic activity (10 mg/kg) and to enhance defeat analgesia (5-10 mg/kg). Although several interpretative frameworks for the current pharmacological profile are considered, it is concluded that full clarification of the substrates of defeat analgesia must await further investigations.