The benzodiazepine receptor antagonists flumazenil and CGS8216 block the enhancement of fear conditioning and interference with escape behavior produced by inescapable shock.

Prior work has suggested that the mediation of the behavioral effects of inescapable shock (IS) might involve release of an endogenous beta-carboline-like ligand at the dorsal raphe nucleus (DRN) that binds to the benzodiazepine (BZ) recognition site on the GABAA complex, thereby disinhibiting the DRN. This was tested by microinjection of the BZ receptor antagonists flumazenil and CGS8216 in the region of the DRN, either before IS or before later behavioral testing. Both compounds blocked subsequent enhancement of fear conditioning and interference with shuttlebox escape when administered before IS, but had no effect when given before testing. In addition, flumazenil did not alter the behavior of escapably shocked subjects.