THE MOUSE DEFENSE TEST BATTERY - EVALUATION OF THE EFFECTS OF NONSELECTIVE AND BZ-1 (OMEGA-1) SELECTIVE, BENZODIAZEPINE RECEPTOR LIGANDS

The behavioral effects of several benzodiazepine (BZ) (omega) receptor ligands were compared using the Mouse Defence Test Battery which has been designed to assess defensive reactions of Swiss mice confronted w ith a natural threat (a rat) and situations associated with this threa t. Primary measures taken before, during and after rat confrontation w ere escape attempts, flight, risk assessment and defensive threat and attack. The drugs used included non-selective BZ (omega) full (clonaze pam, clorazepate, chlordiazepoxide and diazepam) and partial (bretazen il and imidazenil) agonists, and BZ-1 (omega 1) selective (abecarnil, CL, 218,872 and zolpidem) receptor ligands. With the exception of clon azepam, non-selective BZ (omega) receptor compounds only partially aff ected flight behaviors. The drugs reduced some but not all flight meas ures in response to the approaching rat, whereas clonazepam attenuated all flight reactions. In contrast to their mild and inconsistent acti ons on flight, the non-selective BZ omega receptor agonists displayed clear effects on risk assessment when subjects were chased by the rat. When contact was forced between the subject and the rat, the non-sele ctive BZ (omega) receptor full agonists reduced defensive threat and a ttack reaction, while the partial agonists imidazemil and bretazenil o nly weakly attenuated defensive attack behavior. Similarly, after the rat had been removed from the test area, the non-selective BZ (omega) receptor full agonists displayed greater efficacy than the partial ago nists in reducing escape attempts. Overall, results obtained with the selective BZ-1 (omega 1) receptor ligands demonstrated either no clear effects or no specific action on defensive reactions. Taken together, these date demonstrate that: (1) non-selective BZ (omega) agonists di splaying high intrinsic activity affect a wider range of defensive beh aviors that non-selective BZ (omega) receptor partial agonists; (2) th e defense system does not involve primarily BZ (omega) receptors conta ining the alpha 1-subunit.