Benzodiazepine receptors in the periaqueductal grey mediate anti-aversive drug action.

The microinjection of 80, 160 and 320 nmol chlordiazepoxide (CDP) as well as of 20, 40 and 80 nmol midazolam (MDZ) into the dorsal midbrain of rats bearing chronically implanted chemitrodes raised the threshold electrical current inducing escape behaviour by stimulating the dorsal periaqueductal grey matter (DPAG). Parallel linear regressions were obtained by plotting the log dose against drug-induced increases in escape threshold, MDZ being 3.55 times more potent than CDP (95% confidence limits 1.21 and 8.57). Local pretreatment with 80 nmol of the benzodiazepine antagonist Ro 15-1788 blocked the anti-aversive effect of either 160 nmol CDP or 40 nmol MDZ. The same dose of Ro 15-1788 was ineffective when given alone. These results suggest that the anti-aversive action of CDP and MDZ is due to their combination with benzodiazepine receptors in the DPAG.