Role of the central benzodiazepine receptor system in behavioral habituation to novelty.

In this article we report the results of two experiments examining the role of central benzodiazepine receptor sites in the response to novelty. Animals that were food deprived and presented with food in a novel environment showed long latencies before they began eating. Pretreatment with diazepam or preexposure to the "novel" environment for 1 hr/day for 4 or 7 days before testing in that environment dramatically reduced the latency to begin eating. Administration of either the "inverse agonist," FG-7142, or an antagonist, RO15-1788, of the central benzodiazepine receptor before testing completely reversed the effects of 7 days of preexposure to the novel environment. In home-cage feeding tests, FG-7142, but not RO15-1788, increased the latency to begin feeding in food-deprived animals. These findings indicate that FG-7142 is strongly anxiogenic, whereas RO15-1788 is not anxiogenic, yet both drugs are potent in reversing the effects of habituation. The results of these experiments suggest that the normal process of habituation to novelty may involve the release of an endogenous, anxiolytic compound (an agonist) that binds to a central benzodiazepine receptor, the effects of which are blocked by RO15-1788.