INITIAL SUBSENSITIVITY TO ANXIOLYTIC TREATMENTS ON CONFLICT BEHAVIOR IN RATS - PARAMETRIC STUDIES ACROSS DRUG CLASSES

In conflict paradigms, benzodiazepines (BZs) often exhibit maximal ant iconflict effects only after three to four BZ exposures (anxiolytic in itial subsensitivity; AIS). The present experiments examined 1) whethe r AIS occurs with non-BZ anxiolytics and 2) whether prior exposure to non-BZs prevents the occurrence of BZ AIS. Female rats were trained to stable responding levels on a repeated-measures punished drinking par adigm. In Experiment 1, dose-response curves for the effects of the BZ s chlordiazepoxide and diazepam, the barbiturates (BBs) pentobarbital and amobarbital, and the non-BZ, non-BB agent carbamazepine were deter mined in five groups of rats (one group/drug); dose-response curves we re determined on two occasions for each drug. There was an AIS with bo th BZs, with the anticonflict effect being significantly greater for d ose-response determination #2. There was no AIS with the BBs (robust a nd dose-dependent increases in punished responding on both determinati ons) or with carbamazepine (weak anticonflict effect on both determina tions). In Experiment 2, the rats from Experiment 1 received a single- dose challenge with chlordiazepoxide (10 mg/kg). This challenge result ed in a robust anticonflict effect in subjects with a history of repea ted BZ treatment; in contrast, subjects with a history of repeated BB or carbamazepine treatment exhibited smaller anticonflict responses. T hese data suggest that 1) the AIS does not occur with non-BZ anxiolyti cs and 2) the BZ AIS cannot be prevented by repeated exposure to non-B Zs.