THE ANXIOLYTIC-LIKE ACTIVITY OF GR159897, A NON PEPTIDE NK2 RECEPTOR ANTAGONIST, IN RODENT AND PRIMATE MODELS OF ANXIETY

The non-peptide NK2 receptor antagonist, GR159897, was evaluated in tw o putative models of anxiety, the mouse light-dark box and the marmose t human intruder response test. Effects were compared to the structura lly dissimilar NK2 antagonist, (+/-) SR48968 and the benzodiazepines, diazepam and chlordiazepoxide. GR159897 (0.0005-50 mu g/kg SC) caused significant and dose-dependent increases in the amount of time mice sp ent in the more aversive light compartment of the light-dark box, with no effect on locomotor activity. (+/-) SR48968 (0.0005-0.5 mu g/kg SC ) and diazepam (1-1.75 mg/kg SC), also increased time spent in the lig ht compartment, without effect on locomotor activity. In the marmoset human intruder response test, GR159897 (0.2-50 mu g/kg SC) significant ly increased the amount of time marmosets spent at the front of the ca ge during confrontation with a human observer (''threat''). Similar ef fects were produced by (+/-) SR48968 (10-50 mu g/kg SC) and chlordiaze poxide (0.3-3.0 mg/kg SC). These results provide further evidence, in both rodent and primate species, for the ability of NK2 antagonists to restore behaviours which have been suppressed by novel aversive envir onments. Such effects indicate that NK2 antagonists may have anxiolyti c activity.