EVIDENCE FOR CENTRAL BENZODIAZEPINE RECEPTOR HETEROGENEITY FROM BEHAVIOR TESTS

To explore behavioral selectivity as a consequence of multiple recepto r subtypes, four benzodiazepine receptor ligands, flunitrazepam, CGS 9 896, zolpidem, and AHR 11797, were tested at five in vivo endpoints: a nticonvulsant action, anxiolysis/anxiogenesis as determined in the plu s-maze test, locomotor activity, changes in food consumption, and hypo thermia. All compounds produced hypothermia. In the plus-maze test, fl unitrazepam, CGS 9896, and a low dose of zolpidem (0.05 mg/kg) increas ed the time spent in the open arms, although AHR 11797 and higher dose s of zolpidem decreased time spent in the open arms. Flunitrazepam and zolpidem greatly reduced, CGS 9896 slightly reduced, and AHR 11797 di d not affect locomotor activity. Flunitrazepam and CGS 9896 increased food consumption, but AHR 11797 and zolpidem had no effect. Only fluni trazepam fully protected the animals from pentylenetetrazol-induced se izures. The qualitative differences in the effects of these compounds observed are difficult to explain by activation of a single benzodiaze pine receptor subtype. As Ro15-1788 antagonized all the observed effec ts, these compounds act through multiple central benzodiazepine recept ors.