Aggressive and social behavior after alprazolam withdrawal: experimental therapy with Ro 19-8022

The aim of the present study was to ascertain whether withdrawal from alpra zolam can increase anxiety-like and aggressive behavior during intra specie s conflict in mice and, if so, whether a partial benzodiazepine agonist Ro 19-8022 is able to reverse these behavioral changes without untoward effect s such as sedation. An experimental model consisting of interactions of pai rs of singly-housed male mice with non-aggressive group-housed male mice wa s used. Alprazolam(1 mg/kg) was given orally twice daily for 8 days and onc e on the 9th day. When withdrawn from alprazolam (3 days after the last dos e), mice reduced social investigation and increased the incidence of aggres sive behavior in comparison to the pre-withdrawal level. However, the incre ase of aggression was moderate and occurred only in subjects with low pre-t reatment levels of aggression. Ro 19-8022 (10 mg/kg) significantly antagoni zed the decrease of social behavior and the increase of aggression after al prazolam withdrawal without causing sedation or ataxia. (C) 1998 Elsevier S cience Ltd. All rights reserved.